PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3β/CTNNB1 signaling pathway

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Lin, Youcheng ^a   Yang, Zhao ^c,d   Xu, Abai ^a   Dong, Pei ^f   Huang, Yi ^b   Liu, Huan ^e   Li, Feida ^e   Wang, Haifeng ^h   Xu, Qian ⁱ   Wang, Yongqiang ^b   Sun, Da ^e   Zou, Yong ^a   Zou, Xiaowen ^b   Wang, Yu ^a   Zhang, Duo ^e   Liu, Hongjie ^e   Wu, Xun ^a   Zhang, Meng ^b   Fu, Yu ^b   Cai, Zhiming ^b   Liu, Chunxiao ^a   Wu, Song ^b,f,g   more..

^a SOUTHERN MEDICAL UNIVERSITY   (China)

^b THE FIRST AFFILIATED HOSPITAL OF SHENZHEN UNIVERSITY   (China)

^c INSTITUTE OF BIOPHYSICS   (China)

^d UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^e BGI SHENZHEN   (China)

^f SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^g WASHINGTON UNIVERSITY   (United States)

^h KUNMING MEDICAL UNIVERSITY   (China)

ⁱ SOOCHOW UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; CTNNB1 PROTEIN, HUMAN; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3BETA; GSK3B PROTEIN, HUMAN; PHOSPHATIDYLINOSITOL 3 KINASE; PIK3R1 PROTEIN, HUMAN; PROTEIN KINASE B;

CANCER STEM CELL; CELL MOTION; CELL PROLIFERATION; CRISPR CAS SYSTEM; DISEASE COURSE; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; GENE INACTIVATION; GENETICS; HAPLOTYPE; HUMAN; KIDNEY TUMOR; METABOLISM; METASTASIS; NUCLEOTIDE SEQUENCE; PATHOLOGY; PHENOTYPE; PHOSPHORYLATION; SIGNAL TRANSDUCTION; TUMOR CELL LINE; WNT SIGNALING PATHWAY;

BASE SEQUENCE; BETA CATENIN; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; CRISPR-CAS SYSTEMS; DISEASE PROGRESSION; DOWN-REGULATION; EPITHELIAL-MESENCHYMAL TRANSITION; GENE KNOCKOUT TECHNIQUES; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 BETA; HAPLOTYPES; HUMANS; KIDNEY NEOPLASMS; NEOPLASM METASTASIS; NEOPLASTIC STEM CELLS; PHENOTYPE; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; WNT SIGNALING PATHWAY;

EID: 84924778245     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep08997     Document Type: Article

References (47)

1. Rini, B. I., Campbell, S. C. & Escudier, B. Renal cell carcinoma. Lancet 373, 1119-32 (2009).
2. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499, 43-9 (2013).
3. Guo, G. et al. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat Genet 44, 17-9 (2012).
4. Varela, I. et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469, 539-42 (2011).
5. Ather, M. H., Masood, N. & Siddiqui, T. Current management of advanced and metastatic renal cell carcinoma. Urol J 7, 1-9 (2010).
6. Porta, C.& Figlin, R.A. Phosphatidylinositol-3-kinase/Akt signaling pathway and kidney cancer, and the therapeutic potential of phosphatidylinositol-3-kinase/Akt inhibitors. J Urol 182, 2569-77 (2009).
7. Yan, W. et al. PI3 kinase/Akt signaling mediates epithelial-mesenchymal transition in hypoxic hepatocellular carcinoma cells. Biochem Biophys Res Commun 382, 631-6 (2009).
8. Miller, T. W., Rexer, B. N., Garrett, J. T. & Arteaga, C. L. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res 13, 224 (2011).
9. Yuan, T. L. & Cantley, L. C. PI3K pathway alterations in cancer: variations on a theme. Oncogene 27, 5497-510 (2008).
10. Huang, C. H. et al. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science 318, 1744-8 (2007).
11. Fruman, D. A. & Rommel, C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 13, 140-56 (2014).
12. Urick, M. E. et al. PIK3R1 (p85alpha) is somatically mutated at high frequency in primary endometrial cancer. Cancer Res 71, 4061-7 (2011).
13. Jaiswal, B. S. et al . Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation. Cancer Cell 16, 463-74 (2009).
14. Huang, Y. et al.Multilayered molecular profiling supported themonoclonal origin of metastatic renal cell carcinoma. Int J Cancer 135, 78-87 (2014).
15. Philp, A. J. et al. The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res 61, 7426-9 (2001).
16. Taniguchi, C. M. et al. The phosphoinositide 3-kinase regulatory subunit p85alpha can exert tumor suppressor properties through negative regulation of growth factor signaling. Cancer Res 70, 5305-15 (2010).
17. Cizkova, M. et al. PIK3R1 underexpression is an independent prognostic marker in breast cancer. BMC Cancer 13, 545 (2013).
18. Li, L., Plummer, S. J., Thompson, C. L., Tucker, T. C. & Casey, G. Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk. Clin Cancer Res 14, 633-7 (2008).
19. Qian, X. et al. N-cadherin/FGFR promotes metastasis through epithelial-tomesenchymal transition and stem/progenitor cell-like properties. Oncogene 33, 3411-21 (2014).
20. Lee, J. M., Dedhar, S., Kalluri, R. & Thompson, E. W. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172, 973-81 (2006).
21. Kong, D., Li, Y., Wang, Z. & Sarkar, F. H. Cancer Stem Cells and Epithelial-to-Mesenchymal Transition (EMT)-Phenotypic Cells: Are They Cousins or Twins? Cancers (Basel) 3, 716-29 (2011).
22. Jordan, C. T. Cancer stem cell biology: from leukemia to solid tumors. Curr Opin Cell Biol 16, 708-12 (2004).
23. Kondo, T., Setoguchi, T. & Taga, T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A 101, 781-6 (2004).
24. Baccelli, I.&Trumpp, A. The evolving concept of cancer and metastasis stem cells. J Cell Biol 198, 281-93 (2012).
25. Clevers, H. The cancer stem cell: premises, promises and challenges. Nat Med 17, 313-9 (2011).
26. Gassenmaier, M. et al. CXC chemokine receptor 4 is essential for maintenance of renal cell carcinoma-initiating cells and predicts metastasis. Stem Cells 31, 1467-76 (2013).
27. Boumahdi, S. et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature 511, 246-50 (2014).
28. Beck, B. & Blanpain, C. Unravelling cancer stem cell potential. Nat Rev Cancer 13, 727-38 (2013).
29. He, K. et al. Cancer cells acquire a drug resistant, highly tumorigenic, cancer stemlike phenotype through modulation of the PI3K/Akt/beta-catenin/CBP pathway. Int J Cancer 134, 43-54 (2014).
30. Liu, C. et al. Control of beta-catenin phosphorylation/degradation by a dualkinase mechanism. Cell 108, 837-47 (2002).
31. Engelman, J. A., Luo, J. & Cantley, L. C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7, 606-19 (2006).
32. Luo, J. & Cantley, L. C. The negative regulation of phosphoinositide 3-kinase signaling by p85 and it's implication in cancer. Cell Cycle 4, 1309-12 (2005).
33. Xue, G. & Hemmings, B. A. PKB/Akt-dependent regulation of cell motility. J Natl Cancer Inst 105, 393-404 (2013).
34. Bugyi, B. & Carlier, M. F. Control of actin filament treadmilling in cell motility. Annu Rev Biophys 39, 449-70 (2010).
35. Zhu, Q. S. et al. Vimentin is a novel AKT1 target mediating motility and invasion. Oncogene 30, 457-70 (2011).
36. Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-90 (2009).
37. Grille, S. J. et al. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 63, 2172-8 (2003).
38. Tsukamoto, T., Hama, S., Kogure, K. & Tsuchiya, H. Selenate induces epithelialmesenchymal transition in a colorectal carcinoma cell line by AKT activation. Exp Cell Res 319, 1913-21 (2013).
39. Yang, X., Chrisman, H. &Weijer, C. J. PDGF signalling controls the migration of mesoderm cells during chick gastrulation by regulating N-cadherin expression. Development 135, 3521-30 (2008).
40. Zhou, J. et al . 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, 16158-63 (2007).
41. Dubrovska, A. et al. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci U S A 106, 268-73 (2009).
42. Munoz, P., Iliou, M. S. & Esteller, M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol 6, 620-36 (2012).
43. Mani, S. A. et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133, 704-15 (2008).
44. He, K., Xu, T. &Goldkorn, A. Cancer cells cyclically lose and regain drug-resistant highly tumorigenic features characteristic of a cancer stem-like phenotype. Mol Cancer Ther 10, 938-48 (2011).
45. Edge, S. B. & Compton, C. C. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17, 1471-4 (2010).
46. Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819-23 (2013).
47. Qi, L. S. et al. Repurposing CRISPR as an RNA-guided platform for sequencespecific control of gene expression. Cell 152, 1173-83 (2013).