Glycogen synthase kinase-3 inhibition overcomes epithelial-mesenchymal transition-associated resistance to osimertinib inEGFR-mutant lung cancer

被引：23

作者：

Fukuda, Koji ^{[1
,2
]}

Takeuchi, Shinji ^{[1
,2
]}

Arai, Sachiko ^{[1
]}

Kita, Kenji ^{[1
]}

Tanimoto, Azusa ^{[1
]}

Nishiyama, Akihiro ^{[1
]}

Yano, Seiji ^{[1
,2
]}

机构：

[1] Kanazawa Univ, Canc Res Inst, Div Med Oncol, Kanazawa, Ishikawa, Japan

[2] Kanazawa Univ, Nano Life Sci Inst, Kanazawa, Ishikawa, Japan

来源：

CANCER SCIENCE | 2020年 / 111卷 / 07期

关键词：

epidermal growth factor receptor; epithelial-mesenchymal transition; glycogen synthase kinase-3; osimertinib; resistance; GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; EGFR MUTATION; PATHWAY; CHEMOTHERAPY; METASTASIS; MECHANISMS; GEFITINIB; AZD9291; CELLS;

D O I：

10.1111/cas.14454

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, osimertinib, has marked efficacy in patients withEGFR-mutant lung cancer. While epithelial-mesenchymal transition (EMT) plays a role in the resistance to various targeted drugs, its involvement in EGFR-inhibitor resistance remains largely unknown. Preclinical experiments with osimertinib-resistant lung cancer cells showed that EMT was associated with decreased microRNA-200c and increased ZEB1 expression. In several resistant clone cells, pretreatment with the histone deacetylase inhibitor quisinostat helped overcome the resistance by reverting EMT. Furthermore, drug screening from a library of 100 kinase inhibitors indicated that Glycogen synthase kinase-3 (GSK-3) inhibitors, such as LY2090314, markedly inhibited the growth and induced apoptosis of resistant cells, specifically those with a mesenchymal phenotype. These results suggest that GSK-3 inhibition could be useful to circumvent EMT-associated resistance to osimertinib inEGFR-mutant lung cancer.

引用

页码：2374 / 2384

页数：11

共 28 条

[1] EMT: 2016 [J].

Angela Nieto, M. ;

Huang, Ruby Yun-Ju ;

Jackson, Rebecca A. ;

Thiery, Jean Paul .

CELL, 2016, 166 (01) :21-45

[2] JNJ-26481585, a Novel "Second-Generation" Oral Histone Deacetylase Inhibitor, Shows Broad-Spectrum Preclinical Antitumoral Activity [J].

Arts, Janine ;

King, Peter ;

Marien, Ann ;

Floren, Wim ;

Belien, Ann ;

Janssen, Lut ;

Pilatte, Isabelle ;

Roux, Bruno ;

Decrane, Laurence ;

Gilissen, Ron ;

Hickson, Ian ;

Vreys, Veronique ;

Cox, Eugene ;

Bol, Kees ;

Talloen, Willem ;

Goris, Ilse ;

Andries, Luc ;

Du Jardin, Marc ;

Janicot, Michel ;

Page, Martin ;

van Emelen, Kristof ;

Angibaud, Patrick .

CLINICAL CANCER RESEARCH, 2009, 15 (22) :6841-6851

[3] Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor - Mutant lung adenocarcinomas with acquired resistance to kinase inhibitors [J].

Balak, Marissa N. ;

Gong, Yixuan ;

Riely, Gregory J. ;

Somwar, Romel ;

Li, Allan R. ;

Zakowski, Maureen F. ;

Chiang, Anne ;

Yang, Guangli ;

Ouerfelli, Ouathek ;

Kris, Mark G. ;

Ladanyi, Marc ;

Miller, Vincent A. ;

Pao, William .

CLINICAL CANCER RESEARCH, 2006, 12 (21) :6494-6501

[4] Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer [J].

Cai, Xiong ;

Zhai, Hai-Xiao ;

Wang, Jing ;

Forrester, Jeffrey ;

Qu, Hui ;

Yin, Ling ;

Lai, Cheng-Jung ;

Bao, Rudi ;

Qian, Changgeng .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (05) :2000-2009

[5] Tankyrase and the Canonical Wnt Pathway Protect Lung Cancer Cells from EGFR Inhibition [J].

Casas-Selves, Matias ;

Kim, Jihye ;

Zhang, Zhiyong ;

Helfrich, Barbara A. ;

Gao, Dexiang ;

Porter, Christopher C. ;

Scarborough, Hannah A. ;

Bunn, Paul A., Jr. ;

Chan, Daniel C. ;

Tan, Aik Choon ;

DeGregori, James .

CANCER RESEARCH, 2012, 72 (16) :4154-4164

[6] Crystal structure of glycogen synthase kinase 3β:: Structural basis for phosphate-primed substrate specificity and autoinhibition [J].

Dajani, R ;

Fraser, E ;

Roe, SM ;

Young, N ;

Good, V ;

Dale, TC ;

Pearl, LH .

CELL, 2001, 105 (06) :721-732

[7] Discovery of a Potent and Selective EGFR Inhibitor (AZD9291) of Both Sensitizing and T790M Resistance Mutations That Spares the Wild Type Form of the Receptor [J].

Finlay, M. Raymond V. ;

Anderton, Mark ;

Ashton, Susan ;

Ballard, Peter ;

Bethel, Paul A. ;

Box, Matthew R. ;

Bradbury, Robert H. ;

Brown, Simon J. ;

Butterworth, Sam ;

Campbell, Andrew ;

Chorley, Christopher ;

Colclough, Nicola ;

Cross, Darren A. E. ;

Currie, Gordon S. ;

Grist, Matthew ;

Hassall, Lorraine ;

Hill, George B. ;

James, Daniel ;

James, Michael ;

Kemmitt, Paul ;

Klinowska, Teresa ;

Lamont, Gillian ;

Lamont, Scott G. ;

Martin, Nathaniel ;

McFarland, Heather L. ;

Mellor, Martine J. ;

Orme, Jonathon P. ;

Perkins, David ;

Perkins, Paula ;

Richmond, Graham ;

Smith, Peter ;

Ward, Richard A. ;

Waring, Michael J. ;

Whittaker, David ;

Wells, Stuart ;

Wrigley, Gail L. .

JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (20) :8249-8267

[8] Epithelial-to-Mesenchymal Transition Is a Mechanism of ALK Inhibitor Resistance in Lung Cancer Independent of ALK Mutation Status [J].

Fukuda, Koji ;

Takeuchi, Shinji ;

Arai, Sachiko ;

Katayama, Ryohei ;

Nanjo, Shigeki ;

Tanimoto, Azusa ;

Nishiyama, Akihiro ;

Nakagawa, Takayuki ;

Taniguchi, Hirokazu ;

Suzuki, Takeshi ;

Yamada, Tadaaki ;

Nishihara, Hiroshi ;

Ninomiya, Hironori ;

Ishikawa, Yuichi ;

Baba, Satoko ;

Takeuchi, Kengo ;

Horiike, Atsushi ;

Yanagitani, Noriko ;

Nishio, Makoto ;

Yano, Seiji .

CANCER RESEARCH, 2019, 79 (07) :1658-1670

[9] The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J].

Gregory, Philip A. ;

Bert, Andrew G. ;

Paterson, Emily L. ;

Barry, Simon C. ;

Tsykin, Anna ;

Farshid, Gelareh ;

Vadas, Mathew A. ;

Khew-Goodall, Yeesim ;

Goodall, Gregory J. .

NATURE CELL BIOLOGY, 2008, 10 (05) :593-601

[10] EGFR mutation and resistance of non-small-cell lung cancer to gefitinib [J].

Kobayashi, S ;

Boggon, TJ ;

Dayaram, T ;

Janne, PA ;

Kocher, O ;

Meyerson, M ;

Johnson, BE ;

Eck, MJ ;

Tenen, DG ;

Halmos, B .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (08) :786-792

← 1 2 3 →