👤 Junyan Zhuang

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5
Articles
4
Name variants
Also published as: L Zhuang, Y Zhuang, Z. Zhuang
articles
Yongrui Hai, Ruizhuo Lin, Weike Liao +8 more · 2025 · Molecular Biomedicine · BioMed Central · added 2026-04-20
Abstract Cancer cells rely heavily on de novo pyrimidine synthesis. Inhibiting pyrimidine metabolism directly suppresses tumor growth and fosters immune activation within the tumor microenvironment. D Show more
Abstract Cancer cells rely heavily on de novo pyrimidine synthesis. Inhibiting pyrimidine metabolism directly suppresses tumor growth and fosters immune activation within the tumor microenvironment. Dihydroorotate dehydrogenase (DHODH) is a key enzyme in the de novo pyrimidine synthesis pathway. Inhibiting DHODH can reverse immune suppression and trigger a mild innate immune response. However, the impact of DHODH inhibition on natural killer (NK) cells remains to be explored. In this study, we found that DHODH inhibition promoted NK cell infiltration into tumors efficiently. Mechanistically, DHODH suppression induced mitochondrial oxidative stress, leading to mitochondrial DNA (mtDNA) release into the cytoplasm through voltage-dependent anion channel (VDAC) oligomerization and caspase-3 activation. This subsequently activated the stimulator of interferon gene (STING) pathway, triggered ferroptosis, and induced gasdermin E (GSDME) mediated pyroptosis in cancer cells. These changes collectively facilitated NK cell recruitment. Furthermore, infiltrated NK cells enhanced GSDME-dependent pyroptosis in tumor cells through granzyme release, establishing a positive feedback loop that amplified anti-tumor immunity. Additionally, we developed EA6, a novel DHODH inhibitor that is more effective at promoting NK cell infiltration. In summary, this study reveals that targeting pyrimidine metabolism activates a novel mechanism involving pyroptosis-ferroptosis crosstalk and STING pathway activation to enhance NK cell-mediated immunity. These finding opens new avenues for enhancing the efficacy of targeted nucleotide metabolism in cancer therapy. Show less
đź“„ PDF DOI: 10.1186/s43556-025-00339-7
Fe ROS mitochondria synthesis
Yongrui Hai, Renming Fan, Ting Zhao +6 more · 2024 · Pharmacological research · Elsevier · added 2026-04-20
Dihydroorotate dehydrogenase (DHODH)-mediated ferroptosis defense is a targetable vulnerability in cancer. Currently, only a few DHODH inhibitors have been utilized in clinical practice. To further en Show more
Dihydroorotate dehydrogenase (DHODH)-mediated ferroptosis defense is a targetable vulnerability in cancer. Currently, only a few DHODH inhibitors have been utilized in clinical practice. To further enhance DHODH targeting, we introduced the mitochondrial targeting group triphenylphosphine (TPP) to brequinar (BRQ), a robust DHODH inhibitor, resulting in the creation of active molecule B2. This compound exhibits heightened anticancer activity, effectively inhibiting proliferation in various cancer cells, and restraining tumor growth in melanoma xenografts in mice. B2 achieves these effects by targeting DHODH, triggering the formation of reactive oxygen species (ROS), promoting mitochondrial lipid peroxidation, and inducing ferroptosis in B16F10 and A375 cells. Surprisingly, B2 significantly downregulates PD-L1 and alleviates immune suppression. Importantly, B2 exhibits no apparent adverse effects in mice. Collectively, these findings highlight that enhancing the mitochondrial targeting capability of the DHODH inhibitor is a promising therapeutic approach for melanoma treatment. Show less
no PDF DOI: 10.1016/j.phrs.2024.107115
Fe Pd ROS anticancer mitochondria
Shengdong Chen, Shengdong Wang, S Gerstberger +1262 more · 2024 · Cancer Metastasis Reviews · Springer · added 2026-04-20
Shengdong Chen, Shengdong Wang, S Gerstberger, Q Jiang, K Ganesh, D Lyden, CM Ghajar, AL Correia, JA Aguirre-Ghiso, S Cai, M Rescigno, J Massagué, AC Obenauf, J Fares, MY Fares, HH Khachfe, HA Salhab, Y Fares, TS Gerashchenko, AA Schegoleva, AA Khozyainova, EL Choinzonov, EV Denisov, RL Siegel, KD Miller, HE Fuchs, A Jemal, P Bragado, MS Sosa, X Chen, JR Cubillos-Ruiz, B Banushi, SR Joseph, B Lum, JJ Lee, F Simpson, AR Elhamamsy, BJ Metge, HA Alsheikh, LA Shevde, RS Samant, J Yang, A Griffin, Z Qiang, J Ren, M Bedi, M Ray, A Ghosh, DC Wallace, HK Kim, YH Noh, B Nilius, KS Ko, BD Rhee, N Kim, F Randow, RJ Youle, DP Boulton, MC Caino, LX Zampieri, C Silva-Almeida, JD Rondeau, P Sonveaux, R Gundamaraju, W Lu, R Manikam, Y Liu, T Wang, W Ma, Z Jia, Q Wang, M Zhang, R Bai, J Cui, L Sainero-Alcolado, J Liaño-Pons, MV Ruiz-Pérez, M Arsenian-Henriksson, F Bray, M Laversanne, H Sung, J Ferlay, I Soerjomataram, AN Giaquinto, PS Steeg, C Dumontet, JM Reichert, PD Senter, JM Lambert, A Beck, AD Waldman, JM Fritz, MJ Lenardo, J Lu, M Tan, Q Cai, N Weidner, JP Semple, WR Welch, J Folkman, D Fukumura, RK Jain, H Maeda, NC Denko, NH Kim, YH Cha, J Lee, SH Lee, JH Yang, JS Yun, WC Wang, XF Zhang, J Peng, XF Li, AL Wang, YQ Bie, D Ribatti, XL Lou, J Sun, SQ Gong, XF Yu, R Gong, H Deng, RD Schreiber, LJ Old, MJ Smyth, VS LeBleu, JT O’Connell, HK Gonzalez, H Wikman, K Pantel, MC Haigis, X Mao, J Xu, W Wang, C Liang, J Hua, J Liu, R Vessella, XL Gao, YL Tang, XH Liang, D Páez, MJ Labonte, P Bohanes, W Zhang, L Benhanim, Y Ning, K Naidoo, SE Pinder, M Esposito, S Ganesan, Y Kang, K Fizazi, M Carducci, M Smith, R Damião, J Brown, L Karsh, AT Stopeck, A Lipton, JJ Body, GG Steger, K Tonkin, RH de Boer, T Shibue, MW Brooks, RA Weinberg, N Oku, Y Tokudome, C Koike, N Nishikawa, H Mori, I Saiki, L Tentori, AS Dorio, A Muzi, PM Lacal, F Ruffini, P Navarra, S Yamada, XY Bu, V Khankaldyyan, I Gonzales-Gomez, JG McComb, WE Laug, C Manegold, J Vansteenkiste, F Cardenal, W Schuette, PJ Woll, E Ulsperger, A Alva, S Slovin, S Daignault, R Dipaola, K Pienta, KB Kim, V Prieto, RW Joseph, AH Diwan, GE Gallick, NE Papadopoulos, H Vakifahmetoglu-Norberg, AT Ouchida, E Norberg, PJ Burke, PH Willems, R Rossignol, CE Dieteren, MP Murphy, WJ Koopman, EL Mills, B Kelly, L O’Neill, N Borcherding, JR Brestoff, DE Green, N Pfanner, B Warscheid, N Wiedemann, TG Frey, CA Mannella, NS Chandel, CT Walsh, BP Tu, Y Tang, LA Sazanov, IN Watt, MG Montgomery, MJ Runswick, AG Leslie, JE Walker, O WARBURG, R Morais, K Zinkewich-Péotti, M Parent, H Wang, F Babai, M Zollinger, XL Zu, M Guppy, S Bolisetty, EA Jaimes, MD Brand, MR Duchen, SJ Annesley, PR Fisher, Y Wang, H Qi, C Duan, X Liu, T Xia, CL Kuo, BA Ponneri, YC Lin, HW Lien, YK Lo, HY Chou, A Rossi, P Pizzo, R Filadi, R Rizzuto, D De Stefani, A Raffaello, C Mammucari, A Tosatto, R Sommaggio, C Kummerow, RB Bentham, TS Blacker, T Berecz, PE Czabotar, AJ Garcia-Saez, T Vervliet, JB Parys, G Bultynck, C Tse, AR Shoemaker, J Adickes, MG Anderson, J Chen, S Jin, T Oltersdorf, SW Elmore, RC Armstrong, DJ Augeri, BA Belli, SE Weinberg, LA Sena, AP West, W Khoury-Hanold, M Staron, MC Tal, CM Pineda, SM Lang, LV Sinclair, J Rolf, E Emslie, YB Shi, PM Taylor, DA Cantrell, EL Carr, A Kelman, GS Wu, R Gopaul, E Senkevitch, A Aghvanyan, MM Kaminski, SW Sauer, CD Klemke, D Süss, JG Okun, PH Krammer, MM Kamiński, M Kamiński, S Opp, T Ruppert, P Grigaravičius, RJ DeBerardinis, A Mancuso, E Daikhin, I Nissim, M Yudkoff, S Wehrli, WX Zong, JD Rabinowitz, E White, J Fan, JJ Kamphorst, R Mathew, MK Chung, T Shlomi, JW Locasale, AA Khutornenko, VV Roudko, BV Chernyak, AB Vartapetian, PM Chumakov, AG Evstafieva, S Lu, LL Wu, L Yang, J Wang, C Mao, Y Zhang, G Lei, Y Yan, H Lee, L Alberghina, C De Duve, R Wattiaux, S Geisler, KM Holmström, D Skujat, FC Fiesel, OC Rothfuss, PJ Kahle, K Polyak, Y Li, H Zhu, C Lengauer, JK Willson, SD Markowitz, BE Baysal, RE Ferrell, JE Willett-Brozick, EC Lawrence, D Myssiorek, A Bosch, JL Spees, SD Olson, MJ Whitney, DJ Prockop, T Saha, C Dash, R Jayabalan, S Khiste, A Kulkarni, K Kurmi, S Delaunay, G Pascual, B Feng, K Klann, M Behm, A Hotz-Wagenblatt, Z Gan, T Fu, DP Kelly, RB Vega, H Zhou, Z Dai, J Li, X Chang, T Farmer, N Naslavsky, S Caplan, YY Jeong, HH Liu, YT Cao, LL Zhang, F Huang, C Yi, A Picca, J Faitg, J Auwerx, L Ferrucci, D D’Amico, KF Macleod, LP Poole, C Li, X Cheng, H Yuan, S Zhu, Y Zheng, C Huang, L Lu, K Yu, J Zhao, M Chen, C Zhang, Y Zhao, X Yue, H Wu, S Huang, AH Chourasia, K Tracy, C Frankenberger, ML Boland, MN Sharifi, LE Drake, J Okami, DM Simeone, CD Logsdon, C Shi, Y Cai, N Hu, S Ma, E Agarwal, I Bertolini, JH Seo, JC Ghosh, L Wu, D Zhang, L Zhou, Y Pei, Y Zhuang, W Cui, J Liang, Y Yang, L Bai, F Li, E Li, X Sun, H Cao, L Zhan, C Yin, G Wang, P Liang, S Zhao, L Cheng, Y Shi, Q Yun, H Yang, L Li, DB Rivadeneira, DI Gabrilovich, ET Kim, S Herkenne, O Ek, M Zamberlan, A Pellattiero, M Chergova, I Chivite, H Li, H Chang, L Du, J Hai, X Geng, H Tang, S Peng, Y Dong, X Yang, P Yang, M Lin, R Wu, X Wang, B Yang, AJ Levine, C Yan, TS Li, M Murai, M Toyota, H Suzuki, A Satoh, Y Sasaki, K Akino, M Erkan, J Kleeff, I Esposito, T Giese, K Ketterer, MW Büchler, TJ Humpton, B Alagesan, GM DeNicola, D Lu, GN Yordanov, CS Leonhardt, TE O’Sullivan, LR Johnson, HH Kang, JC Sun, Z Chen, L Liu, Q Cheng, M Giacomello, A Pyakurel, C Glytsou, L Scorrano, W Chen, H Zhao, AP Trotta, JE Chipuk, J Zhang, M Yu, Y Xie, Y Huang, DW Wolff, YC Chae, AV Kossenkov, YG Lee, HY Tang, D Karimi, N Pedram, F Kakaei, M Asadi, E Poursaei, TA Kermani, X Zhang, T Song, B Wu, Z Zhang, TE Li, D Xu, Y Zhu, BY Hu, B Cunniff, AJ McKenzie, NH Heintz, AK Howe, A Aguinaldo, E Wait, KG Bryant, JN Moloney, TG Cotter, JM Cameron, M Gabrielsen, YH Chim, J Munro, EJ McGhee, D Sumpton, H Alshaabi, N Shannon, R Gravelle, S Milczarek, T Messier, DC Altieri, D Liu, Y Gao, J Yin, Y Feng, PK Melwani, BN Pandey, N Rabas, S Palmer, L Mitchell, S Ismail, A Gohlke, JS Riley, G Pinto, C Brou, C Zurzolo, Z Nahacka, R Zobalova, M Dubisova, J Rohlena, J Neuzil, J Novak, SP Desai, SN Bhatia, M Toner, D Irimia, Q Li, L Yao, Y Wei, S Geng, C He, H Jiang, J Pasquier, BS Guerrouahen, TH Al, P Ghiabi, M Maleki, N Abu-Kaoud, T Ahmad, S Mukherjee, B Pattnaik, M Kumar, S Singh, L Ippolito, A Morandi, ML Taddei, M Parri, G Comito, A Iscaro, JC Chang, HS Chang, YC Wu, WL Cheng, TT Lin, HJ Chang, CU Kidwell, JR Casalini, S Pradeep, SD Scherer, D Greiner, D Bayik, SJ Hanna, K McCoy-Simandle, E Leung, A Genna, J Condeelis, D Cox, F Xu, E Yinwang, Y Xue, EI Buzas, K Takenaga, N Koshikawa, H Nagase, H Mou, F Guan, X Wu, J Zhou, Y Lin, Y He, C Fan, E Abad, A Lyakhovich, C Salaud, A Alvarez-Arenas, F Geraldo, J Belmonte-Beitia, GF Calvo, C Gratas, T Delvaeye, P Vandenabeele, L Leybaert, DV Krysko, J Ariazi, A Benowitz, V De Biasi, ML Den Boer, S Cherqui, H Cui, R Schulz, PM Görge, A Görbe, P Ferdinandy, PD Lampe, Y Yao, XL Fan, D Jiang, X Li, ZB Xu, D Ren, P Zheng, S Zou, Y Gong, J Duan, I Saenz-de-Santa-Maria, P Chastagner, E Perthame, C Delmas, C Toulas, DR Welch, C Foster, I Rigoutsos, P Huang, Z Wang, W Xu, H Simonnet, N Alazard, K Pfeiffer, C Gallou, C Béroud, J Demont, Y Wan, Q Zou, LM Tseng, PH Yin, CW Chi, CY Hsu, CW Wu, LM Lee, WY Hung, AF Li, SH Li, CC Hsu, HC Lee, YH Wei, Y Yuan, YS Ju, Y Kim, CJ Yoon, H Tu, J Gu, QH Meng, J Kim, JW Davis, RL Correia, SM Oba-Shinjo, M Uno, N Huang, SK Marie, WW Jiang, B Masayesva, M Zahurak, AL Carvalho, E Rosenbaum, E Mambo, MM Kim, JD Clinger, BG Masayesva, PK Ha, ML Zahurak, WH Westra, CS Lin, SC Chang, LS Wang, TY Chou, WH Hsu, DH Lee, JH Lee, DK Kim, DY Keum, JG Dai, ZY Zhang, QX Liu, JX Min, E Reznik, ML Miller, Y Şenbabaoğlu, N Riaz, J Sarungbam, SK Tickoo, L Moro, AA Arbini, E Marra, M Greco, D Kazdal, A Harms, V Endris, R Penzel, M Kriegsmann, F Eichhorn, S Chaudhary, S Ganguly, A Singh, JK Palanichamy, A Chopra, R Bakhshi, J Boultwood, C Fidler, KI Mills, PM Frodsham, R Kusec, A Gaiger, A Cormio, F Guerra, G Cormio, V Pesce, F Fracasso, V Loizzi, KS Vikramdeo, S Anand, MA Khan, M Khushman, MJ Heslin, G Pietka, W Kukwa, E Bartnik, A Scińska, AM Czarnecka, Z Tian, Q Yang, B Shi, P Hou, G Amuthan, G Biswas, HK Ananadatheerthavarada, C Vijayasarathy, HM Shephard, NG Avadhani, Y Xu, PK Kopinski, LN Singh, S Zhang, MT Lott, DJ Tan, RK Bai, LJ Wong, A Chatterjee, D Sidransky, JB Stewart, B Alaei-Mahabadi, R Sabarinathan, T Samuelsson, J Gorodkin, CM Gustafsson, KL Hertweck, S Dasgupta, MY Kim, H Kim, JA Sung, J Koh, S Cho, DH Chung, K Kaneva, D Merkurjev, D Ostrow, A Ryutov, P Triska, K Stachelek, K Tsuji, Y Kida, S Yamamoto, Y Shinozaki, T Watanabe, H Takeuchi, A Fujimoto, DS Hoon, KE de Visser, JA Joyce, N Ron-Harel, D Santos, JM Ghergurovich, PT Sage, A Reddy, SB Lovitch, MN Serasinghe, SY Wieder, TT Renault, R Elkholi, JJ Asciolla, JL Yao, T Yu, BS Jhun, Y Yoon, C Schwindling, A Quintana, E Krause, M Hoth, L Simula, F Nazio, S Campello, H Kong, M Song, B Zhang, L Zhang, Z Li, S Lin, T Zheng, B Hao, K Sinha, J Das, PB Pal, PC Sil, A Peña-Blanco, AJ García-Sáez, GR Bantug, C Hess, CH Chang, JD Curtis, LJ Maggi, B Faubert, AV Villarino, D O’Sullivan, M Philip, A Schietinger, N Dumauthioz, B Tschumi, M Wenes, B Marti, F Franco, NE Scharping, AV Menk, RS Moreci, RD Whetstone, RE Dadey, SC Watkins, MD Buck, GR Klein, DE Sanin, YR Yu, H Imrichova, T Chao, Z Xiao, M Gao, SA Vardhana, MA Hwee, M Berisa, DK Wells, KE Yost, B King, J Ogando, ME Sáez, J Santos, C Nuevo-Tapioles, M Gut, A Esteve-Codina, DS Thommen, VH Koelzer, P Herzig, A Roller, M Trefny, S Dimeloe, JC Beltra, S Manne, MS Abdel-Hakeem, M Kurachi, JR Giles, P Vignali, BR Ford, NL Rittenhouse, AC Scott, F Dündar, P Zumbo, SS Chandran, CA Klebanoff, M Shakiba, I Vitale, G Manic, LM Coussens, G Kroemer, L Galluzzi, X Geeraerts, J Fernández-Garcia, FJ Hartmann, KE de Goede, L Martens, Y Elkrim, R Xu, H Gu, E Zhang, J Qu, W Cao, MN Hasan, O Capuk, SM Patel, D Sun, Y Han, SY Rodriguez, S Siddiqui, C Treese, G Di Conza, CH Tsai, H Gallart-Ayala, L Zaffalon, PS Liu, T Teav, S Christen, RE Menjivar, ZC Nwosu, W Du, KL Donahue, HS Hong, C Espinoza, Z He, M Huang, T Liu, H Xu, R Kalluri, C Sun, Z Qin, LM Becker, AP Vo, MP Cain, D Tampe, L Bizarro, T Fiaschi, A Marini, E Giannoni, P Gandellini, A De Donatis, SJ Parker, CR Amendola, K Hollinshead, Q Yu, K Yamamoto, J Encarnación-Rosado, CM Sousa, DE Biancur, CJ Halbrook, MH Sherman, A Achreja, TL Yeung, LS Mangala, C Han, TD Bhagat, D Von Ahrens, M Dawlaty, Y Zou, J Baddour, M Bacci, A Angelin, L Gil-de-Gómez, S Dahiya, J Jiao, L Guo, MH Levine, MJ Watson, SJ Mullett, AE Overacre-Delgoffe, RM Peralta, S Grebinoski, J Qiu, T Noguchi, Y Luo, J Ma, L Qi, T Knifley, DW Piecoro, P Rychahou, S Li, W Dai, W Mo, J Feng, S Andrzejewski, SP Gravel, M Pollak, J St-Pierre, K Rohlenova, K Sachaphibulkij, J Stursa, A Bezawork-Geleta, J Blecha, B Endaya, LF Dong, VJ Jameson, D Tilly, L Prochazka, K Valis, L Song, C Liu, Q Zhang, X Liang, C Ramachandran, PK Nair, A Alamo, CB Cochrane, E Escalon, SJ Melnick, MK Shin, YD Jeon, SH Hong, SH Kang, JY Kee, JS Jin, L Dang, K Yen, EC Attar, D Rohle, J Popovici-Muller, N Palaskas, S Turcan, C Grommes, C Campos, A Alistar, BB Morris, R Desnoyer, HD Klepin, K Hosseinzadeh, C Clark, TS Pardee, K Lee, J Luddy, C Maturo, R Rodriguez, S Isom, C Xie, J Jin, X Bao, WH Zhan, TY Han, M Gan, O Tusskorn, T Khunluck, A Prawan, L Senggunprai, V Kukongviriyapan, ND Nguyen, D Lin, TN Fujimoto, JM Molkentine, T Peng, H Fu, Y Guo, P Hu, J Shi, P Yuan, W Yu, J Lin, A Xu, X Xu, LC Nava, S Tiberti, PA Corsetto, F Conte, P Tyagi, M Machwirth, A Jaccard, T Wyss, N Maldonado-Pérez, ST Teoh, A Lepez, H Yan, DW Parsons, G Jin, R McLendon, BA Rasheed, W Yuan, C Bardella, PJ Pollard, I Tomlinson, M Bolzoni, M Chiu, F Accardi, R Vescovini, I Airoldi, P Storti, J Márquez, FJ Alonso, JM Matés, JA Segura, M Martín-Rufián, JA Campos-Sandoval, MI Gross, SD Demo, JB Dennison, L Chen, T Chernov-Rogan, B Goyal, A Le, AN Lane, M Hamaker, S Bose, A Gouw, J Barbi, Y Xiang, ZE Stine, J Xia, Y Lu, RS O’Connor, BJ Altman, A Cassidy-Stone, E Ingerman, C Song, C Yoo, T Kuwana, A Ruiz, E Alberdi, C Matute, J Chwa, ME Oh, T Abeywardana, Q Xie, Q Wu, CM Horbinski, WA Flavahan, K Yang, W Zhou, MH You, MJ Jeon, SR Kim, WK Lee, SY Cheng, G Jang, SA Rosenberg, P Sharma, S Hu-Lieskovan, JA Wargo, A Ribas, D Wang, H Yu, F Zhou, H Zhang, AD Garg, A Kaczmarek, O Krysko, P Agostinis, EJ Lee, GH Nam, NK Lee, M Kih, E Koh, YK Kim, S Pierini, C Fang, S Rafail, JG Facciponte, J Huang, F De Sanctis, S Pustylnikov, F Costabile, S Beghi, A Facciabene, C Wei, O Yeku, RJ Brentjens, JC Yang, CH June, SR Riddell, TN Schumacher, ML Davila, I Riviere, J Park, LG Cowell, X Si, M Shao, X Teng, G Xiao, H Huang, M Sukumar, GU Mehta, SJ Patel, R Roychoudhuri, JG Crompton, NS Joshi, A Chandele, HK Lee, DR Urso, J Hagman, L Gattinoni, NP Restifo, K Klein, K He, AI Younes, HB Barsoumian, D Chen, T Ozgen, B Kalyanaraman, G Cheng, J Zielonka, O Ouari, M Lopez, D McAllister, K Boyle, LL Bu, GT Yu, WW Deng, L Mao, JF Liu, SR Ma Show less
Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical inv Show more
Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical involvement of specific mitochondrial-associated events, including mitochondrial quality control, intercellular mitochondrial transfer, and mitochondrial genetics, in potentiating the metastatic cascade of neoplastic cells. Furthermore, numerous recent studies have consistently emphasized the highly significant role mitochondria play in coordinating the regulation of tumor-infiltrating immune cells and immunotherapeutic interventions. This review provides a comprehensive and rigorous scholarly investigation of this subject matter, exploring the intricate mechanisms by which mitochondria contribute to tumor metastasis and examining the progress of mitochondria-targeted cancer therapies. Show less
đź“„ PDF DOI: 10.1007/s10555-024-10211-9
mitochondria review
Li Xing, Shaohui Wang, H Sung +944 more · 2023 · Cell Death Discovery · Nature · added 2026-04-20
Li Xing, Shaohui Wang, H Sung, J Ferlay, RL Siegel, M Laversanne, I Soerjomataram, A Jemal, C Xia, X Dong, H Li, M Cao, D Sun, S He, W Cao, HD Chen, YW Yu, N Li, WQ Chen, BC Bade, CS Dela Cruz, AH Nielsen, U Fredberg, F Wu, L Wang, C Zhou, MI Toki, K Harrington, KN Syrigos, R Rosell, N Karachaliou, O Arrieta, RS Herbst, D Morgensztern, C Boshoff, ZF Lim, PC Ma, J Liu, M Hong, Y Li, D Chen, Y Wu, Y Hu, SJ Dixon, KM Lemberg, MR Lamprecht, R Skouta, EM Zaitsev, CE Gleason, J Li, F Cao, HL Yin, ZJ Huang, ZT Lin, N Mao, DH Manz, NL Blanchette, BT Paul, FM Torti, SV Torti, Y Mou, J Wang, J Wu, D He, C Zhang, C Duan, RS Hotchkiss, A Strasser, JE McDunn, PE Swanson, DL Vaux, D Moujalled, JR Liddell, ML Coleman, EA Sahai, M Yeo, M Bosch, A Dewar, MF Olson, M Suzanne, H Steller, X Chen, PB Comish, D Tang, R Kang, JR Hunt, MK Georgieff, IV Milto, IV Suhodolo, VD Prokopieva, TK Klimenteva, DJ Lane, AM Merlot, ML Huang, DH Bae, PJ Jansson, S Sahni, MW Hentze, MU Muckenthaler, B Galy, C Camaschella, D Galaris, A Barbouti, K Pantopoulos, T Nakamura, I Naguro, H Ichijo, C Yu, W Hou, Y Xie, X Song, X Sun, MT Lotze, HJ Zeh, A Donovan, CA Lima, JL Pinkus, GS Pinkus, LI Zon, S Robine, M Kruszewski, HB Dunford, A Hamaï, M Mehrpour, LJ Su, JH Zhang, H Gomez, R Murugan, X Hong, D Xu, S Doll, M Conrad, S Zalba, TL Ten Hagen, MP Wymann, R Schneiter, MM Gaschler, BR Stockwell, D Li, H Kuwata, S Hara, VE Kagan, G Mao, F Qu, JP Angeli, CS Croix, GE Winter, LS Musavi, ED Lee, B Snijder, M Rebsamen, P Vishnupriya, A Aparna, VP Viswanadha, WS Yang, KJ Kim, M Patel, MS Shchepinov, NK Singh, GN Rao, Y Zou, ET Graham, AA Deik, JK Eaton, W Wang, B Yan, Y Ai, Q Sun, Y Ma, Y Cao, H Lv, C Zhen, P Yang, L Hu, P Shang, J Lewerenz, SJ Hewett, Y Huang, M Lambros, PW Gout, PW Kalivas, H Sato, H Imai, M Matsuoka, T Kumagai, T Sakamoto, T Koumura, R SriRamaratnam, ME Welsch, K Shimada, VS Viswanathan, P Koppula, L Zhuang, B Gan, X Wang, Z Huang, Y Zhou, J Xia, W Hu, R Kong, N Wang, W Han, W Bao, J Lu, K Bersuker, JM Hendricks, Z Li, L Magtanong, B Ford, PH Tang, FP Freitas, R Shah, M Aldrovandi, MC da Silva, I Ingold, E Mishima, J Ito, Z Wu, A Wahida, C Mao, X Liu, Y Zhang, G Lei, Y Yan, H Lee, M Soula, RA Weber, O Zilka, H Alwaseem, K La, F Yen, VAN Kraft, CT Bezjian, S Pfeiffer, L Ringelstetter, C Müller, F Zandkarimi, J Vasquez-Vivar, Z Shi, S Tan, R Brigelius-Flohé, C Wang, Z Yang, Y Bai, T Shukuya, ME Poh, J Ni, K Chen, J Zhang, X Zhang, S Sui, L Zhang, S Xu, Z Wang, X Tian, Y Yang, L Ma, X Pan, Z Lin, D Jiang, Y Yu, D Yang, H Zhou, FJ Li, HZ Long, ZW Zhou, HY Luo, SG Xu, LC Gao, Z Fan, G Yang, W Zhang, Q Liu, G Liu, P Liu, L Feng, K Zhao, L Sun, X Yin, C Liu, M Chen, Y Jiang, Y Sun, X Wu, Z Sui, H Zhang, Y Wang, Z Yu, X Ji, J Qian, SMJ Rahman, PJ Siska, BK Harris, L Bai, L Zhi, Q Zhao, Y Chen, H Tian, J Jin, KR Zhang, YF Zhang, HM Lei, YB Tang, CS Ma, QM Lv, Y Xu, D Lv, C Yan, H Su, Y Shi, K Wang, J He, C Tu, H Xu, Y Lv, F He, L Antonucci, M Karin, E Panieri, L Saso, J Yang, Z Zhao, B Cao, S Yu, S Sajadimajd, M Khazaei, Z Ou, R Chen, X Niu, D Wu, J Duan, H Xiao, L Zhao, YP Kang, A Mockabee-Macias, C Jiang, A Falzone, N Prieto-Farigua, E Stone, W Liu, W Duan, J Song, S Wei, S Xia, H Wang, Q Huang, S Cheng, D Pei, B Proneth, YY Tyurina, E Panzilius, S Kobayashi, HL Zhang, BX Hu, ZL Li, T Du, JL Shan, ZP Ye, R Sha, C Yuan, X Sheng, J Peng, S Li, F Li, C Lv, QK Yang, H Wu, A Liu, J Hou, X Wen, C Li, S Xiong, T Yue, X Yang, X Hu, N Guo, YS Guan, Q He, Q Zou, L Yang, W Cui, Y Liu, QR Sun, L Jiang, N Kon, T Li, SJ Wang, T Su, H Hibshoosh, W Gu, G Kroemer, C Huang, M Yang, J Deng, P Li, W Su, R Jiang, W Yang, X He, Z Zhang, X Zheng, KR Marshall, M Gong, L Wodke, JH Lamb, DJ Jones, PB Farmer, L Kondiparthi, A Jo, JH Bae, YJ Yoon, TH Chung, EW Lee, YH Kim, JY Song, J Marszalek, EA Craig, EM Terzi, VO Sviderskiy, SW Alvarez, GC Whiten, R Possemato, T Papagiannakopoulos, AL Moreira, S Adams, KM Fujihara, BZ Zhang, TD Jackson, MO Ogunkola, B Nijagal, JV Milne, X Ye, C 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W Du, S Gao, D Wei, YQ Ke, P Duan, L Zhou, CY Wang, P Cao, Q Chen, Q Pan, H Gao, X Zhong, LS Kristensen, TB Hansen, MT Venø, J Kjems, G Shan, MS Andersen, LVW Stagsted, KK Ebbesen, FA Karreth, PP Pandolfi, Y Luo, Q Zhang, B Lv, Y Shang, O Li, J Kang, JJ Zhang, LW Hu, L Li, W Shanshan, M Hongying, F Jingjing, Y Yiming, R Yu, Y Rui, C Pan, K Wei, J Huang, Z Guo, Y Niu, X Xu, WX Peng, P Koirala, YY Mo, H Lu, S Wu, P Kim, X Zhou, J Yao, R Li, S Su, D Ye, W Lu, X Li, X Sui, N Hu, P Wang, G Xiu, M Wang, L Ouyang, W Lai, C Gai, M Yu, J Zheng, N Zhang, M Xu, T Chen, D Priem, G van Loo, MJM Bertrand, C Gao, F Xiao, Z Aburjania, S Jang, J Whitt, R Jaskula-Stzul, H Chen, JB Rose, J Xiao, M Liu, B Lian, N Vu, M Kim, D Stephenson, H MacKnight, C Chalfant, X Zeng, D Lu, M Yin, M Shan, Y Gao, S Liu, S Yan, J Zhu, R Lu, C Kang, K Tang, B Xu, Q Han, Y Xia, C Gong, AA Abdelgalil, HM Alkahtani, FI Al-Jenoobi, G Blumenschein, E Lachaier, C Louandre, C Godin, Z Saidak, M Baert, M Diouf, L Freire Boullosa, J Van Loenhout, T Flieswasser, J De Waele, C Hermans, H Lambrechts, W Zhou, M Yan, S Lian, K Sun, W Wu, Z Geng, H Bai, T Liu, B Zhang, H Yu, Z Han, Z Xu, C An, L Xu, H Xin, J Kryczka, KH Czarnecka-Chrebelska, E Brzeziańska-Lasota, L Galluzzi, L Senovilla, I Vitale, J Michels, I Martins, O Kepp, Z Liang, W Zhao, L Meng, Z Cui, C Abdel Shaheed, GE Ferreira, A Dmitritchenko, AJ McLachlan, RO Day, B Saragiotto, D Ding, J Laengle, J Kabiljo, L Hunter, J Homola, S Prodinger, G Egger, T Zhang, B Sun, C Zhong, K Xu, P Hofman, H Yan, H Liu, C Wu, LF Ye, KR Chaudhary, AD Harken, CJ Kinslow, PS Upadhyayula, CH Hsieh, HC Hsieh, FS Shih, PW Wang, LX Yang, DB Shieh, G Zhu, H Chi, Y Yin, H Diao, Z Liu, C Ge, S Zhang, H Mu, S Zheng, Z Tan, X Huang, US Neill, T Efferth, G Chen, F Benthani, D Liang, Z Bian, X Dai, W Chen, S Mo, H Yi, H Yao, L Lu, G He, M Wu, B Yuan, F Liao, Y Ren, X Deng, T Yang, N Han, X Peng, Q Ma, OA Ahmed Hamdi, SN Syed Abdul Rahman, K Awang, N Abdul Wahab, CY Looi, NF Thomas, R Zhang, T Pan, Y Xiang, M Zhang, H Xie, SW Ng, Y Chan, DK Chellappan, T Madheswaran, F Zeeshan, YL Chan, Y Fan, B Han, F Chen, S Alakurtti, T Mäkelä, S Koskimies, J Yli-Kauhaluoma, WY Yan, J Cai, JN Wang, YS Gong, XB Ding, KS Prabhu, AA Bhat, KS Siveen, S Kuttikrishnan, SS Raza, T Raheed, R Xu, J Tian, W Teng, D Boulghobra, PE Grillet, M Laguerre, M Tenon, J Fauconnier, P Fança-Berthon, M Shao, Q Jiang, C Shen, L Qiu, L Zhu, Y Lu, Z Sun, J Han, YY Zeng, YB Luo, XD Ju, YJ Cui, YB Pan, W Koch, W Kukula-Koch, Z Marzec, E Kasperek, L Wyszogrodzka-Koma, W Szwerc, Y Tsai, JC Merritt, SD Richbart, EG Moles, AJ Cox, KC Brown, SL Miles, K Srinivasan, XY Liu, DG Wei, RS Li, Q Wu, J Feng, L Yan, HQ Zhang, XF Xie, GM Li, JR Chen, MT Li, SL Morris-Natschke, KH Lee, CY Wu, YH Yang, YS Lin, GH Chang, MS Tsai, CM Hsu, S Chen, Y Guo, R Zhao, M Jiang, H Fu, UM Nazim, JK Jeong, SY Park, Q Gao, L Gu, A Gepdiremen, V Mshvildadze, H Süleyman, R Elias, D Wang, Y Lou, P Huang, M Jin, M Adnan, A Rasul, G Hussain, MA Shah, MK Zahoor, H Anwar, JS Lou, LP Zhao, ZH Huang, XY Chen, JT Xu, WC Tai, P Waiwut, A Inujima, H Inoue, I Saiki, H Sakurai, B Jiang, M Wan, A Vanduchova, P Anzenbacher, E Anzenbacherova, M Russo, C Spagnuolo, GL Russo, K Skalicka-Woźniak, M Daglia, E Sobarzo-Sánchez, Y Iida, M Okamoto-Katsuyama, S Maruoka, K Mizumura, T Shimizu, S Shikano, SM Lee, BS Bae, HW Park, NG Ahn, BG Cho, YL Cho, FG Zhai, QC Liang, YY Wu, JQ Liu, JW Liu, F Huang, J Pang, W Niu, YY Zhao, YQ Yang, HH Sheng, Q Tang, L Han, SM Wang, L Zeng, L Lignitto, SE LeBoeuf, H Homer, S Jiang, M Askenazi, TR Karakousi, M Yamamoto, TW Kensler, H Motohashi, W Cheng, M Guo, M Shen, D Kong, J Shao, C Liang, L Mahoney-Sánchez, H Bouchaoui, S Ayton, D Devos, JA Duce, JC Devedjian Show less
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, Show more
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer. Show less
đź“„ PDF DOI: 10.1038/s41420-023-01407-z
Fe ROS review
T. Narayan, A. Dutta, A. Agarwal +541 more · 2022 · iScience · Elsevier · added 2026-04-20
T. Narayan, A. Dutta, A. Agarwal, R.J. MacKenzie, R. Pippa, C.A. Eide, J. Oddo, J.W. Tyner, R. Sears, M.P. Vitek, M.D. Odero, D.J. Christensen, B.J. Druker, A. Ashkenazi, R.C. Pai, S. Fong, S. Leung, D.A. Lawrence, S.A. Marsters, C. Blackie, L. Chang, A.E. McMurtrey, A. Hebert, A. Bene, T.C. Chambers, I. Beuvink, A. Boulay, S. Fumagalli, F. Zilbermann, S. Ruetz, T. O'Reilly, F. Natt, J. Hall, H.A. Lane, G. Thomas, M. Bhat, N. Robichaud, L. Hulea, N. Sonenberg, J. Pelletier, I. Topisirovic, R. Briffa, S.P. Langdon, G. Grech, D.J. Harrison, B.A. Carneiro, W.S. El-Deiry, T.C. Chou, A.E. Collier, D.F. Spandau, R.C. Wek, I. Cristobal, R. Manso, R. Rincón, C. Caramés, C. Senin, A. Borrero, J. Martínez-Useros, M. Rodriguez, S. Zazo, O. Aguilera, R. Rincon, C. Carames, J. Madoz-Gurpide, F. Rojo, J. Garcia-Foncillas, R.M. De Palma, S.R. Parnham, Y. Li, J.J. Oaks, Y.K. Peterson, Z.M. Szulc, B.M. Roth, Y. Xing, B. Ogretmen, D. Deng, K. Shah, M.J. Fournier, L. Coudert, S. Mellaoui, P. Adjibade, C. Gareau, M.F. Côté, R.C. Gaudreault, R. Mazroui, A.M. Gaben, C. Saucier, M. Bedin, V. Barbu, J. Mester, C. Filion, D. Martel, Y. Labelle, A.G. Georgakilas, O.A. Martin, W.M. Bonner, M.J. Gerdes, C.J. Sevinsky, A. Sood, S. Adak, M.O. Bello, A. Bordwell, A. Can, A. Corwin, S. Dinn, R.J. Filkins, M. Gorospe, X. Wang, K.Z. Guyton, N.J. Holbrook, M.M. Gottesman, J.R. Graff, B.W. Konicek, J.H. Carter, E.G. Marcusson, R.S. Herbst, S.G. Eckhardt, R. Kurzrock, S. Ebbinghaus, P.J. O'Dwyer, M.S. Gordon, W. Novotny, M.A. Goldwasser, T.M. Tohnya, B.L. Lum, S.D. Heys, K.G. Park, M.A. McNurlan, A.G. Calder, V. Buchan, K. Blessing, O. Eremin, P.J. Garlick, B. Hoang, A. Benavides, Y. Shi, Y. Yang, P. Frost, J. Gera, A. Lichtenstein, A.N. Hobden, E. Cundliffe, N. Ikoma, K. Raghav, G. Chang, A. Ishitsuka, E. Fujine, Y. Mizutani, C. Tawada, H. Kanoh, Y. Banno, M. Seishima, S. Iwasaki, N.T. Ingolia, S.C. Jahn, P.E. Corsino, B.J. Davis, M.E. Law, P. Nørgaard, B.K. Law, V. Janssens, S. Longin, J. Goris, M.A. Jensen, V. Ferretti, R.L. Grossman, L.M. Staudt, Y.H. Jin, K.J. Yoo, Y.H. Lee, S.K. Lee, A. Kahvejian, Y.V. Svitkin, R. Sukarieh, M.N. M'Boutchou, S.K. Kelley, L.A. Harris, D. Xie, L. Deforge, K. Totpal, J. Bussiere, J.A. Fox, S.L. Kim, Y.C. Liu, Y.R. Park, S.Y. Seo, S.H. Kim, I.H. Kim, S.O. Lee, S.T. Lee, D.G. Kim, S.W. Kim, N.N. Kreis, F. Louwen, J. Yuan, M. Law, E. Forrester, A. Chytil, P. Corsino, G. Green, B. Davis, T. Rowe, B. Law, S.L. Lehman, G.J. Cerniglia, G.J. Johannes, J. Ye, S. Ryeom, C. Koumenis, S. Lek, J. Vargas-Medrano, E. Villanueva, B. Marcus, W. Godfrey, R.G. Perez, J. Lemke, S. von Karstedt, J. Zinngrebe, H. Walczak, D. Leonard, W. Huang, S. Izadmehr, C.M. O'Connor, D.D. Wiredja, Z. Wang, N. Zaware, Y. Chen, D.M. Schlatzer, J. Kiselar, V. Leung-Pineda, C.E. Ryan, H. Piwnica-Worms, L. Li, J. Wang, J.G. Li, Z. Wu, P. Ma, X.J. Lian, I.E. Gallouzi, H. Lin, X. Qiu, B. Zhang, J. Zhang, T.A. Lin, X. Kong, T.A.J. Haystead, A. Pause, G. Belsham, J.C. Lawrence, J. Lu, J.S. Kovach, F. Johnson, J. Chiang, R. Hodes, R. Lonser, Z. Zhuang, M. Mahyar-Roemer, K. Roemer, A. Maiuthed, C. Ninsontia, K. Erlenbach-Wuensch, B. Ndreshkjana, J.K. Muenzner, A. Caliskan, H. Ahmed P, A.P. Husayn, C. Chaotham, A. Hartmann, K. Malinowsky, U. Nitsche, K.P. Janssen, F.G. Bader, C. Spath, E. Drecoll, G. Keller, H. Hofler, S. Mazhar, S.E. Taylor, J. Sangodkar, G. Narla, K. McClinch, R.A. Avelar, D. Callejas, D. Wiredja, A. Perl, D.B. Kastrinsky, D. Schlatzer, M. Cooper, D.R. McIlwain, T. Berger, T.W. Mak, N. Melling, R. Simon, J.R. Izbicki, L.M. Terracciano, C. Bokemeyer, G. Sauter, A.H. Marx, J.R. Mills, Y. Hippo, F. Robert, S.M.H. Chen, A. Malina, C.J. Lin, U. Trojahn, H.G. Wendel, A. Charest, R.T. Bronson, C.S. Mitsiades, S.P. Treon, N. Mitsiades, Y. Shima, P. Richardson, R. Schlossman, T. Hideshima, K.C. Anderson, K. Morita, S. He, R.P. Nowak, M.W. Zimmerman, C. Fu, A.D. Durbin, M.W. Martel, N. Prutsch, N.S. Gray, S. Narayan, A.S. Jaiswal, R. Sharma, A. Nawab, L.V. Duckworth, M. Zajac-Kaye, T.J. George, J. Sharma, A.K. Sharma, R.A. Hromas, S. Ramisetti, A. Singh-Pillay, P. Singh, S. Amin, P. Palaiologos, D. Chrysikos, S. Theocharis, G. Kouraklis, G.J. Belsham, A.C. Gingras, O. Donzé, M.D. Ralff, P.G. Richardson, C. Eng, J. Kolesar, N.R. Rodrigues, A. Rowan, M.E. Smith, I.B. Kerr, W.F. Bodmer, J.V. Gannon, D.P. Lane, H.K. Roy, B.F. Olusola, D.L. Clemens, W.J. Karolski, A. Ratashak, H.T. Lynch, T.C. Smyrk, E. Rozengurt, H.P. Soares, J. Sinnet-Smith, P.P. Ruvolo, R. Tohme, E.K. Schmidt, G. Clavarino, M. Ceppi, P. Pierre, R.R. Sharma, T.S. Ravikumar, D. Raimo, W.L. Yang, R.L. Siegel, K.D. Miller, H.E. Fuchs, A. Jemal, J.C. Soria, Z. Márk, P. Zatloukal, B. Szima, I. Albert, E. Juhász, J.L. Pujol, J. Kozielski, N. Baker, D. Smethurst, W. Stöcklein, W. Piepersberg, A. Surov, P. Clauser, Y.W. Chang, L. Martincich, S.C. Partridge, J.Y. Kim, H.J. Meyer, A. Wienke, A. Suzuki, T. Ito, H. Kawano, M. Hayashida, Y. Hayasaki, Y. Tsutomi, K. Akahane, T. Nakano, M. Miura, K. Shiraki, T. Araki, S. Tahmasebi, T. Alain, V.K. Rajasekhar, J.P. Zhang, M. Prager-Khoutorsky, A. Khoutorsky, Y. Dogan, C.G. Gkogkas, E. Petroulakis, A. Sylvestre, A. Thorburn, K. Behbakht, H. Ford, H. Tian, E.K. Wittmack, T.J. Jorgensen, R. Tohmé, S. Gandhe, G. Tabaro, S. Vallabhaneni, A. Thomas, N. Vasireddi, N.S. Dhawan, A. Ma'ayan, N. Sharma, C. Vaklavas, S.W. Blume, W.E. Grizzle, K. Van der Jeught, H.C. Xu, Y.J. Li, X.B. Lu, G. Ji, A. Montinaro, R.E. Miller, K. Ariail, B. Gliniak, T.S. Griffith, M. Kubin, W. Chin, J. Jones, A. Woodward, T. Le, H. Wang, Y. Liu, J. Ding, Y. Huang, J. Liu, N. Liu, Y. Ao, Y. Hong, L. Wang, L. Zhang, M. Wang, E. Yaaghubi, A.F. Ghilardi, R.B. Ferreira, C.W. Chiang, O.A. Guryanova, D. Kopinke, C.D. Heldermon, S.S. Wang, E.D. Esplin, J.L. Li, L. Huang, A. Gazdar, J. Minna, G.A. Evans, X.W. Wang, Y.J. Zhang, J.S. Warmus, G.J. Dilley, A.I. Meyers, F. Wei, Y. Zhang, L. Geng, P. Zhang, G. Wang, R.H. Weiss, J. Westermarck, N. Wu, Z. Du, Y. Zhu, Y. Song, L. Pang, Z. Chen, J. Xu, P. Wang, H. Yang, J. Zhou, X. Li, W. Xue, C. Yu, Y. Tian, F. Zhu, J.Y. Zhou, W.Z. Wei, G.S. Wu, S.Q. Xu, P. Yaffee, A. Osipov, C. Tan, R. Tuli, A. Hendifar, L. Yong, Z. YuFeng, B. Guang, P.E. Young, C.M. Womeldorph, E.K. Johnson, J.A. Maykel, B. Brucher, A. Stojadinovic, I. Avital, A. Nissan, S.R. Steele, Y. Yu, S.S. Kanwar, B.B. Patel, J. Nautiyal, F.H. Sarkar, A.P. Majumdar, B. Fang, N. Fujita, T. Tsuruo, X. Zhou, W. Liu, X. Hu, A. Dorrance, R. Garzon, P.J. Houghton, C. Shen Show less
Summary The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but these tumors quickly develop resistance to this treatment. We have observed increased phosphorylation of AKT1/mTO Show more
Summary The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but these tumors quickly develop resistance to this treatment. We have observed increased phosphorylation of AKT1/mTOR/4EBP1 and levels of p21 in FOLFOX-resistant CRC cells. We have identified a small molecule, NSC49L, that stimulates protein phosphatase 2A (PP2A) activity, downregulates the AKT1/mTOR/4EBP1-axis, and inhibits p21 translation. We have provided evidence that NSC49L- and TRAIL-mediated sensitization is synergistically induced in p21-knockdown CRC cells, which is reversed in p21-overexpressing cells. p21 binds with procaspase 3 and prevents the activation of caspase 3. We have shown that TRAIL induces apoptosis through the activation of caspase 3 by NSC49L-mediated downregulation of p21 translation, and thereby cleavage of procaspase 3 into caspase 3. NSC49L does not affect global protein synthesis. These studies provide a mechanistic understanding of NSC49L as a PP2A agonist, and how its combination with TRAIL sensitizes FOLFOX-resistant CRC cells. Show less
đź“„ PDF DOI: 10.1016/j.isci.2022.104518
amino-acid synthesis