p120-catenin suppresses proliferation and tumor growth of oral squamous cell carcinoma via inhibiting nuclear phospholipase C-γ1 signaling.

Abstract

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-β-catenin complex has been shown to mediate calcium-induced keratinocyte differentiation via inducing activation of plasma membrane phospholipase C-γ1 (PLC-γ1). On the other hand, PLC-γ1 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-γ1, we examined effects of p120 knockdown or p120 and PLC-γ1 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-γ1 in the plasma membrane and increased levels of PLC-γ1 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-γ1 or knockdown of PLC-γ1 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-γ1 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-γ1.

• Authors: Lusha Li, Shangli Ji, Chandrama Shrestha, Yi Jiang, Liyan Liao, Feng Xu, Zhenming Liu, Daniel D Bikle, Zhongjian Xie
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 235 Issue 12 Pg. 9399-9413 (12 2020) ISSN: 1097-4652 [Electronic] United States
• PMID: 32356317 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Calcium, Dietary
• Catenins
• Epidermal Growth Factor
• Phospholipase C gamma

Topics

• Calcium, Dietary (pharmacology)
• Carcinoma, Squamous Cell (pathology)
• Catenins (metabolism, pharmacology)
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Epidermal Growth Factor (metabolism)
• Head and Neck Neoplasms (drug therapy, metabolism)
• Mouth Neoplasms (drug therapy, pathology)
• Phospholipase C gamma (drug effects, metabolism)
• Signal Transduction (drug effects)
• Squamous Cell Carcinoma of Head and Neck (metabolism, pathology)