👤 Y Morita

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Also published as: K. Morita,
articles

Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A

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

Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance

NN Cotte, CB Thompson, R Iurlaro +94 more · 2018 · Nature communications · Nature · added 2026-04-20
Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer. However, the significance of LD accumulation in colorectal cancer (CRC) biology is incompletely understood under chemothera Show more
Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer. However, the significance of LD accumulation in colorectal cancer (CRC) biology is incompletely understood under chemotherapeutic conditions. Since drug resistance is a major obstacle to treatment success, we sought to determine the contribution of LD accumulation to chemotherapy resistance in CRC. Here we show that LD content of CRC cells positively correlates with the expression of lysophosphatidylcholine acyltransferase 2 (LPCAT2), an LD-localised enzyme supporting phosphatidylcholine synthesis. We also demonstrate that LD accumulation drives cell-death resistance to 5-fluorouracil and oxaliplatin treatments both in vitro and in vivo. Mechanistically, LD accumulation impairs caspase cascade activation and ER stress responses. Notably, droplet accumulation is associated with a reduction in immunogenic cell death and CD8 + T cell infiltration in mouse tumour grafts and metastatic tumours of CRC patients. Collectively our findings highlight LPCAT2-mediated LD accumulation as a druggable mechanism to restore CRC cell sensitivity. Show less
đź“„ PDF DOI: 10.1038/s41467-017-02732-5
immunogenic synthesis