期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 235, 期 12, 页码 9399-9413出版社
WILEY
DOI: 10.1002/jcp.29744
关键词
cell proliferation and differentiation; p120-catenin; phospholipase C-gamma 1; squamous cell carcinoma cells (OSCC)
资金
- National Natural Science Foundation of China [81072219, 81272973, 81471055, 81672646]
- National Institutes of Health [1R03DE018001, 1R21DE019529-01A2, R01AR050023]
p120-catenin (p120) serves as a stabilizer of the calcium-dependent cadherin-catenin complex and loss of p120 expression has been observed in several types of human cancers. The p120-dependent E-cadherin-beta-catenin complex has been shown to mediate calcium-induced keratinocyte differentiation via inducing activation of plasma membrane phospholipase C-gamma 1 (PLC-gamma 1). On the other hand, PLC-gamma 1 has been shown to interact with phosphatidylinositol 3-kinase enhancer in the nucleus and plays a critical role in epidermal growth factor-induced proliferation of oral squamous cell carcinoma (OSCC) cells. To determine whether p120 suppresses OSCC proliferation and tumor growth via inhibiting PLC-gamma 1, we examined effects of p120 knockdown or p120 and PLC-gamma 1 double knockdown on proliferation of cultured OSCC cells and tumor growth in xenograft OSCC in mice. The results showed that knockdown of p120 reduced levels of PLC-gamma 1 in the plasma membrane and increased levels of PLC-gamma 1 and its signaling in the nucleus in OSCC cells and OSCC cell proliferation as well as xenograft OSCC tumor growth. However, double knockdown of p120 and PLC-gamma 1 or knockdown of PLC-gamma 1 alone did not have any effect. Immunohistochemical analysis of OSCC tissue from patients showed a lower expression level of p120 and a higher expression level of PLC-gamma 1 compared with that of adjacent noncancerous tissue. These data indicate that p120 suppresses OSCC cell proliferation and tumor growth by inhibiting signaling mediated by nuclear PLC-gamma 1.
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