Nutlin-3 inhibits epithelial-mesenchymal transition by interfering with canonical transforming growth factor-β1-Smad-Snail/Slug axis

Cancer Letters

Volumn 342, Issue 1, 2014, Pages 82-91

  Wu, Yeping ^a   Fu, Yingying ^a   Zheng, Lin ^a   Lin, Guanyu ^a   Ma, Jian ^a   Lou, Jianshu ^a   Zhu, Hong ^a   He, Qiaojun ^a   Yang, Bo ^a  

^a ZHEJIANG UNIVERSITY   (China)

Author keywords

EMT; Nutlin 3; Smad pathway; TGF 1

Indexed keywords

GEFITINIB; LAPATINIB; NUTLIN 3; SMAD2 PROTEIN; SMAD3 PROTEIN; TRANSCRIPTION FACTOR SLUG; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA1; UVOMORULIN;

ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BINDING AFFINITY; CANCER CELL; CELL MIGRATION; CELL MOTILITY; CONTROLLED STUDY; DOWN REGULATION; DRUG CYTOTOXICITY; DRUG MECHANISM; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; HUMAN CELL; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; TRANSCRIPTION REGULATION; UPREGULATION;

EMT; NUTLIN-3; SMAD PATHWAY; TGF-Β1;

ANTINEOPLASTIC AGENTS; CADHERINS; CELL LINE, TUMOR; CELL MOVEMENT; DRUG EVALUATION, PRECLINICAL; DRUG SYNERGISM; EPITHELIAL-MESENCHYMAL TRANSITION; GENE EXPRESSION; HUMANS; IMIDAZOLES; PHOSPHORYLATION; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTEIN PROCESSING, POST-TRANSLATIONAL; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RNA, MESSENGER; SIGNAL TRANSDUCTION; SMAD PROTEINS; TRANSCRIPTION FACTORS; TRANSFORMING GROWTH FACTOR BETA1; UP-REGULATION;

EID: 84887617467     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2013.08.039     Document Type: Article

References (50)

1. Garber Ken Epithelial-to-mesenchymal transition is important to metastasis, but questions remain. J. Natl. Cancer Inst. 2008, 100:232-239.
2. Tsuji Takanori, Ibaragi Soichiro, Guo-fu Hu Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res. 2009, 69:7135-7139.
3. Pardali Katerina, Moustakas Aristidis Actions of TGF-β as tumor suppressor and pro-metastatic factor in human cancer. Biochim. Biophys. Acta. 2007, 1775:21-62.
4. Massagué Joan, Seoane Joan, Wotton David Smad transcription factors. Genes Dev. 2005, 19:2783-2810.
5. Ladanyi Marc, Cha Charles, Lewis Ronald, Jhanwar Suresh C., Huvos Andrew G., Healey John H. MDM2 Gene amplification in metastatic osteosarcoma. Cancer Res. 1993, 53:16-18.
6. Wallander Michelle L., Tripp Sheryl, Layfield Lester J. MDM2 amplification in malignant peripheral nerve sheath tumors correlates with p53 protein expression. Arch Pathol Lab Med. 2012, 136:95-99.
7. Moskovits Neta, Kalinkovich Alexander, Bar Jair, Lapidot Tsvee, Oren Moshe P53 attenuates cancer cell migration and invasion through repression of SDF-1/CXCL12 expression in stromal fibroblasts. Cancer Res. 2006, 66:10671-10676.
8. Lyubomir T. Vassilev, MDM2 inhibitors for cancer therapy. Trends in Mol. Med. 2007, 13:23-31.
9. Muller Patricia A.J., Vousden Karen H., Norman Jim C. p53 and its mutants in tumor cell migration and invasion. J. Cell Biol. 2011, 192:209-218.
10. Supiot Stéphane, Hill Richard P., Bristow Robert G. Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol. Cancer Ther. 2008, 7:993-999.
11. Valentine Jane M., Kumar Sonia, Moumen Abdeladim A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation. BMC Cancer 2011, 11:79-90.
12. Li Q.Q., Xu J.D., Wang W.J., Cao X.X., Chen Q., Tang F., Chen ZhQ, Liu X.P., Xu Z.D. Twist1-mediated Adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin. Cancer Res. 2009, 15:2657-2665.
13. Arumugam Thiruvengadam, Ramachandran Vijaya, Fournier Keith F., Wang Huamin, Marquis Lauren, Abbruzzese James L., Gallick Gary E., Logsdon Craig D., McConkey David J., Choi Woonyoung Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009, 69:5820-5828.
14. Michaelis1 M, Rothweiler F, Barth S, Cinatl J, Rikxoort M van, Löschmann N, Voges Y, Breitling R, Deimling A von, Rodel F., Weber K., Fehse B., Mack E., Stiewe T., Doerr H.W., Speidel D., Cinatl J. Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells. Cell Death Dis. 2011, (2):243-251.
15. Maerken Tom Van, Ferdinande Liesbeth, Taildeman Jasmien, Lambertz Irina, Yigit Nurten, Vercruysse Liesbeth, Rihani Ali, Michaelis Martin, Cinatl Jindrich, Cuvelier Claude A., Marine Jean-Christophe, Paepe Anne De, Bracke Marc, Speleman Frank, Vandesompele Jo Antitumor activity of the selective MDM2 antagonist Nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J. Natl. Cancer Inst. 2009, (101):1562-1574.
16. Derynck Rik, Goeddel David V., Ullrich Axel, Gutterman Jordan U., Williams Richard D., Bringman Timothy S., Berger Wendy H. Synthesis of messenger RNAs for transforming growth factors α and β and the epidermal growth factor receptor by human tumors. Cancer Res. 1987, (47):707-712.
17. Leckband Deborah, Sivasankar Sanjeevi Cadherin recognition and adhesion. Curr. Opin. Cell Biol. 2012, (24):620-627.
18. Halder Sunil K., Daniel Beauchamp R., Datta Pran K. A specific inhibitor of TGF-B receptor kinase, SB-431542, as a potent antitumor agent for human cancers. Neoplasia 2005, (7):509-521.
19. Hay Elizabeth D. The Mesenchymal Cell, Its role in the embryo, and the remarkable signaling mechanisms that create it. Dev. Dyn. 2005, (233):706-720.
20. Bolós Victoria, Peinado Hector, Pérez-Moreno Mirna A., Fraga Mario F., Esteller Manel, Cano Amparo The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J. Cell Sci. 2002, (116):499-511.
21. Peinado Hector, Quintanilla Miguel, Cano Amparo Transforming growth factor beta 1 induces Snail transcription factor in epithelial cell lines. Mechanisms for epithelial mesenchymal transitions. J. Biol. Chem. 2003, (278):21113-211123.
22. Valcourt Ulrich, Kowanetz Marcin, Niimi Hideki, Heldin Carl-Henrik, Moustakas Aristidis TGF-β and the smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol. Biol. Cell 2005, (16):1987-2002.
23. Brandl Martina, Seidler Barbara, Haller Ferdinand, Adamski Jerzy, Schmid Roland M., Saur1 Dieter, Schneider Günter IKK controls canonical TGF -SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in Panc1 cells. J. Cell Sci. 2010, (123):4231-4239.
24. Jia J., Zhang Wi, Liu J.Y., Chen G., Liu H., Zhong H.Y., Liu B., Cai Y., Zhang J.L., Zhao Y.F. Epithelial mesenchymal transition is required for acquisition of anoikis resistance and metastatic potential in adenoid cystic carcinoma. PLOS ONE 2012, (7):51549-51562.
25. Thompson Erik W., Newgreen Donald F. Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition. Cancer Res. 2005, (65):5991-5995.
26. Uramoto Hidetaka, Iwata Teruo, Onitsuka Takamitsu, Shimokawa Hidehiko, Hanagiri Takeshi, Oyama Tsunehiro Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung adenocarcinoma. Anticancer Res. 2010, (30):2513-2518.
27. Chung Jin-Haeng, Rho Jin Kyung, Xu Xianhua, Lee Jong Seok, Yoon Ho Il, Lee Choon Taek, Choi Yun Jung, Kim Hye-Ryoun, Kim Cheol Hyeon, Lee Jae Cheol Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs. Lung Cancer 2011, (73):176-182.
28. Chang Tzu-Hua, Tsai Meng-Feng, Su Kang-Yi, Wu Shang-Gin, Huang Cheng-Po, Yu Sung-Liang, Yu Yung-Luen, Lan Chou-Chin, Yang Chih-Hsin, Lin Shwu-Bin, Wu1 Chin-Pyng, Shih Jin-Yuan, Yang Pan-Chyr Slug confers resistance to the epidermal growth factor receptor tyrosine kinase inhibitor. Am. J. Respir. Crit. Care Med. 2011, (183):1071-1079.
29. Witta Samir E., Gemmill Robert M., Hirsch Fred R., Coldren Christopher D., Hedman Karla, Ravdel Larisa, Helfrich Barbara, Dziadziuszko Rafal, Chan Daniel C., Sugita Michio, Chan Zeng, Baron Anna, Franklin Wilbur, Drabkin Harry A., Girard Luc, Gazdar Adi F., Minna John D., Bunn Paul A., Restoring Jr. E-Cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res. 2006, (66):944-950.
30. Coldren Christopher D., Helfric h Barbara A., Witta Samir E., Sugita Michio, Lapadat Razvan, Zeng Chan, Baron Anna, Franklin Wilbur A., Hirsch Fred R., Geraci Mark W., Bunn Paul A., Jr. Baseline gene expression predicts sensitivity to gefitinib in non-small cell lung cancer cell lines. Mol. Cancer Res. 2006, (4):521-528.
31. Yauch Robert L., Januario Thomas, Eberhard David A., Cavet Guy, hu Wenjing, Fu Ling, Pham ThinhQ., Soriano Robert, Stinson Jeremy, Seshagiri Somasekar, Modrusan Zora, Lin Chin-Yu, O'Neill Vincent, Amler Lukas C. Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin. Cancer Res. 2005, (11):8686-8698.
32. Maerken Tom Van, Ferdinande Liesbeth, Taildeman Jasmien, Lambertz Irina, Yigit Nurten, Vercruysse Liesbeth, Rihani Ali, Michaelis Martin, Jr.Jindrich Cinatl, Cuvelier Claude A., Marine Jean-Christophe, Paepe Anne De, Bracke Marc, Speleman Frank, Vandesompele Jo Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J. Natl. Cancer Inst. 2009, (101):1562-1574.
33. Schoppy David W., Brown Eric J. Chk'ing p53-deficient breast cancers. J. Clin. Invest. 2012, (122):1202-1205.
34. Fu H., Hu ZhL, Wen J.F., Wang K.S., Liu Y TGF-β promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways. Acta Biochim. Biophys. Sin. 2009, (41):648-656.
35. Mohammad Khalid S., Javelaud Delphine, Fournier Pierrick G.J., Niewolna Maria, Ryan McKenna C., Peng Xiang H., Duong Vu, Dunn Lauren K., Mauviel Alain, A Theresa Guise TGF-β-RI Kinase Inhibitor SD-208 Reduces the Development and Progression of Melanoma Bone Metastases. Cancer Res. 2011, (71):175-184.
36. Graauw Marjo de, van Miltenburg Martine H., Schmidt Marjanka K., Pont Chantal, Lalai Reshma, Kartopawiro Joelle, Pardali Evangelia, Le Dévédec Sylvia E., Smit Vincent T., Wal Annemieke van der, Van't Veer Laura J., Cleton-Jansen Anne-Marie, Dijke Peter ten, Water Bob van de Annexin A1 regulates TGF-β signaling and promotes metastasis formation of basal-like breast cancer cells. Proc. Natl. Acad. Sci. 2008, (107):6340-6345.
37. Rao ZY, Cai MY, Yang GF, He LR, Mai SJ, Hua WF, Liao YJ, Deng HX, Chen YCh, Guan XY, Zeng YX, Kung Hsiang-Fu, Xie D EZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-β1 and is a predictor of outcome in ovarian carcinoma patients. Carcinogenesis 2010, (31):1576-1583.
38. Ao Mingfang, Williams Karin, Bhowmick Neil A., Hayward Simon W. Transforming Growth Factor-β Promotes Invasion in Tumorigenic but not in Nontumorigenic Human Prostatic Epithelial Cells. Cancer Res. 2006, (66):8007-8016.
39. Do Thuy-Vy, Kubba Lena A., Du Hongyan, Sturgis Charles D., Woodruff Teresa K. Transforming growth factor-β1, transforming growth factor-β2 and transforming growth factor-β3 enhance ovarian cancer metastatic potential by inducing a smad3-dependent epithelial-to-mesenchymal transition. Mol. Cancer Res. 2008, (6):695-705.
40. Oft Martin, Heider Karl-Heinz, Beug Hartmut TGFβ signaling is necessary for carcinoma cell invasiveness and metastasis. Curr. Biol. 1998, (8):1243-1252.
41. Eawabata Masahiro, Miyazono Kohei Signal transduction of the TGF-β superfamily by smad proteins. J. Biol. Chem. 1999, (125):9-16.
42. Xu J, Lamouille Samy, Derynck Rik TGF-β-induced epithelial to mesenchymal transition. Cell Research 2009, (19):156-172.
43. Chen YL, Lv J, Ye XL, Sun MY, Xu Q, Liu ChH, Min LH, Li HP, Liu P, Ding XY Sorafenib inhibits transforming growth factor β1-mediated epithelial-mesenchymal transition and apoptosis in mouse hepatocytes. Hepatology 2011, (53):1708-1718.
44. Nagai Tomoyuki, Arao Tokuzo, Furuta Kazuyuki, Sakai Kazuko, Kudo Kanae, Kaneda Hiroyasu, Tamura Daisuke, Aomatsu Keiichi, Kimura Hideharu, Fujita Yoshihiko, Matsumoto Kazuko, Saijo Nagahiro, Kudo Masatoshi, Nishio Kazuto Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma. Mol. Cancer Ther. 2011, (10):169-177.
45. Yoshikawa Masahiro, Hishikawa Keiichi, Marumo Takeshi, Fujita Toshiro Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by Tgf-β1 in human renal epithelial cells. J. Am. Soc. Nephrol. 2007, (18):58-65.
46. Araki Shinako, Eitel Jacob A., Batuello Christopher N., Bijangi-Vishehsaraei Khadijeh, Xie Xian-Jin, Danielpour David, Pollok Karen E., Boothman David A., Mayo Lindsey D. TGF-β1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer. J. Clin. Invest. 2010, (120):290-302.
47. McConkey David J., Choi Woonyoung, Marquis Lauren, Martin Frances, Williams Michael B., Shah Jay, Svatek Robert, Das Aditi, Adam Liana, Kamat Ashish, Siefker-Radtke Arlene, Dinney Colin Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 2009, (28):335-344.
48. Fuchs Bryan C., Fujii Tsutomu, Dorfman Jon D., Goodwin Jonathan M., Zhu Andrew X., Lanuti Michael, Tanabe Kenneth K. Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res. 2008, (68):2391-2399.
49. Frederick Barbara A., Helfrich Barbara A., Coldren Christopher D., Zheng Di, Chan Dan, Bunn Paul A., Jr., Raben David Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Mol. Cancer Ther. 2007, (6):1683-1691.
50. Witta1 S.E., Dziadziuszko R., Yoshida K., Hedman K., Varella-Garcia M., Bunn P.A., Hirsch F.R. ErbB-3 expression is associated with E-cadherin and their coexpression restores response to gefitinib in non-small-cell lung cancer (NSCLC). Ann. Oncol. 2009, (20):689-695.