An IL6-STAT3 loop mediates resistance to PI3K inhibitors by inducing epithelial-mesenchymal transition and cancer stem cell expansion in human breast cancer cells

Biochemical and Biophysical Research Communications

Volumn 453, Issue 3, 2014, Pages 582-587

  Yang, Lin ^a   Han, Siqi ^b   Sun, Yong ^c  

^a Hubei Maternal and Child Health Hospital   (China)

^b JINLING HOSPITAL   (China)

^c NANJING MEDICAL UNIVERSITY   (China)

Author keywords

Breast cancer; Cancer stem cell; Epithelial mesenchymal transition; PI3K inhibitor; PIK3CA; Resistance

Indexed keywords

INTERLEUKIN 6; PHOSPHATIDYLINOSITOL 3 KINASE; STAT3 PROTEIN; ENZYME INHIBITOR; STAT3 PROTEIN, HUMAN;

APOPTOSIS; ARTICLE; BREAST CANCER; CANCER STEM CELL; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; FEEDBACK SYSTEM; FLOW CYTOMETRY; HUMAN; HUMAN CELL; PHENOTYPE; POSITIVE FEEDBACK; REAL TIME POLYMERASE CHAIN REACTION; UPREGULATION; WESTERN BLOTTING; ANTAGONISTS AND INHIBITORS; BREAST TUMOR; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; TUMOR CELL LINE;

BREAST NEOPLASMS; CELL LINE, TUMOR; ENZYME INHIBITORS; ENZYME-LINKED IMMUNOSORBENT ASSAY; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; INTERLEUKIN-6; NEOPLASTIC STEM CELLS; PHOSPHATIDYLINOSITOL 3-KINASES; REAL-TIME POLYMERASE CHAIN REACTION; STAT3 TRANSCRIPTION FACTOR;

EID: 84918521700     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2014.09.129     Document Type: Article

References (23)

1. L.C. Cantley, The phosphoinositide 3-kinase pathway, Science 296 (2002) 1655-1657.
2. T.L. Yuan, L.C. Cantley, PI3K pathway alterations in cancer: variations on a theme, Oncogene 27 (2008) 5497-5510.
3. D.A. Levine, F. Bogomolniy, C.J. Yee, A. Lash, R.R. Barakat, P.I. Borgen, J. Boyd, Frequent mutation of the PIK3CA gene in ovarian and breast cancers, Clin. Cancer Res. 11 (2005) 2875-2878.
4. J. Zheng, X. Zou, J. Yao, The antitumor effect of GDC-0941 alone and in combination with rapamycin in breast cancer cells, Chemotherapy 58 (2012) 273-281.
5. Y. Ando, M. Inada-Inoue, A. Mitsuma, T. Yoshino, A. Ohtsu, N. Suenaga, M. Sato, T. Kakizume, M. Robson, C. Quadt, T. Doi, Phase I dose-escalation study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in Japanese patients with advanced solid tumors, Cancer Sci. 105 (2014) 347-353.
6. J. Rodon, I. Brana, L.L. Siu, M.J. De Jonge, N. Homji, D. Mills, E. Di Tomaso, C. Sarr, L. Trandafir, C. Massacesi, F. Eskens, J.C. Bendell, Phase I dose-escalation and - expansion study of buparlisib (BKM120), an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors, Invest. New Drugs 32 (2014) 670-681.
7. L.A. Byers, L. Diao, J. Wang, P. Saintigny, L. Girard, M. Peyton, L. Shen, Y. Fan, U. Giri, P.K. Tumula, M.B. Nilsson, J. Gudikote, H. Tran, R.J. Cardnell, D.J. Bearss, S.L. Warner, J.M. Foulks, S.B. Kanner, V. Gandhi, N. Krett, S.T. Rosen, E.S. Kim, R.S. Herbst, G.R. Blumenschein, J.J. Lee, S.M. Lippman, K.K. Ang, G.B. Mills, W.K. Hong, J.N. Weinstein Wistuba II, K.R. Coombes, J.D. Minna, J.V. Heymach, An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance, Clin. Cancer Res. 19 (2013) 279-290.
8. M. Al-Hajj, M.S. Wicha, A. Benito-Hernandez, S.J. Morrison, M.F. Clarke, Prospective identification of tumorigenic breast cancer cells, Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 3983-3988.
9. H. Korkaya, G.I. Kim, A. Davis, F. Malik, N.L. Henry, S. Ithimakin, A.A. Quraishi, N. Tawakkol, R. D'Angelo, A.K. Paulson, S. Chung, T. Luther, H.J. Paholak, S. Liu, K.A. Hassan, Q. Zen, S.G. Clouthier, M.S. Wicha, Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population, Mol. Cell 47 (2012) 570-584.
10. H.A. Smith, Y. Kang, The metastasis-promoting roles of tumor-associated immune cells, J. Mol. Med. (Berl.) 91 (2013) 411-429.
11. A. Jarnicki, T. Putoczki, M. Ernst, Stat3: linking inflammation to epithelial cancer - more than a "gut" feeling?, Cell Div 5 (2010) 14.
12. C. Zhou, J. Liu, Y. Tang, X. Liang, Inflammation linking EMT and cancer stem cells, Oral Oncol. 48 (2012) 1068-1075.
13. N.J. Sullivan, A.K. Sasser, A.E. Axel, F. Vesuna, V. Raman, N. Ramirez, T.M. Oberyszyn, B.M. Hall, Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells, Oncogene 28 (2009) 2940-2947.
14. G. Xie, Q. Yao, Y. Liu, S. Du, A. Liu, Z. Guo, A. Sun, J. Ruan, L. Chen, C. Ye, Y. Yuan, IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures, Int. J. Oncol. 40 (2012) 1171-1179.
15. G. Ligresti, L. Militello, L.S. Steelman, A. Cavallaro, F. Basile, F. Nicoletti, F. Stivala, J.A. McCubrey, M. Libra, PIK3CA mutations in human solid tumors: role in sensitivity to various therapeutic approaches, Cell Cycle 8 (2009) 1352-1358.
16. J.A. Engelman, Targeting PI3K signalling in cancer: opportunities, challenges and limitations, Nat. Rev. Cancer 9 (2009) 550-562.
17. P. Mallini, T. Lennard, J. Kirby, A. Meeson, Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem cells and drug resistance, Cancer Treat. Rev. 40 (2014) 341-348.
18. S.E. Witta, R.M. Gemmill, F.R. Hirsch, C.D. Coldren, K. Hedman, L. Ravdel, B. Helfrich, R. Dziadziuszko, D.C. Chan, M. Sugita, Z. Chan, A. Baron, W. Franklin, H.A. Drabkin, L. Girard, A.F. Gazdar, J.D. Minna, P.A. Bunn Jr., Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines, Cancer Res. 66 (2006) 944-950.
19. X. Li, M.T. Lewis, J. Huang, C. Gutierrez, C.K. Osborne, M.F. Wu, S.G. Hilsenbeck, A. Pavlick, X. Zhang, G.C. Chamness, H. Wong, J. Rosen, J.C. Chang, Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy, J. Natl Cancer Inst. 100 (2008) 672-679.
20. T. Bachelot, I. Ray-Coquard, C. Menetrier-Caux, M. Rastkha, A. Duc, J.Y. Blay, Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients, Br. J. Cancer 88 (2003) 1721-1726.
21. J. Zhou, J. Wulfkuhle, H. Zhang, P. Gu, Y. Yang, J. Deng, J.B. Margolick, L.A. Liotta, E. Petricoin 3rd, Y. Zhang, Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance, Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 16158-16163.
22. M. Sen, S. Joyce, M. Panahandeh, C. Li, S.M. Thomas, J. Maxwell, L. Wang, W.E. Gooding, D.E. Johnson, J.R. Grandis, Targeting Stat3 abrogates EGFR inhibitor resistance in cancer, Clin. Cancer Res. 18 (2012) 4986-4996.
23. B. Dai, J. Meng, M. Peyton, L. Girard, W.G. Bornmann, L. Ji, J.D. Minna, B. Fang, J.A. Roth, STAT3 mediates resistance to MEK inhibitor through microRNA miR-17, Cancer Res. 71 (2011) 3658-3668.