Restoring E-cadherin-mediated cell–cell adhesion increases PTEN protein level and stability in human breast carcinoma cells

• Published in: Biochemical and biophysical research communications Vol. 363; no. 1; pp. 165 - 170
• Main Authors: Li, Zengxia, Wang, Liying, Zhang, Wen, Fu, Yi, Zhao, Hongbo, Hu, Yali, Prins, Bram Peter, Zha, Xiliang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.11.2007
• Subjects: 60 APPLIED LIFE SCIENCES; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Cadherins - metabolism; CARCINOMAS; Cell Adhesion; Cell Line, Tumor; Cell–cell adhesion; CHROMOSOMES; Degradation; E-cadherin; Enzyme Stability; GROWTH; Humans; MAMMARY GLANDS; METASTASES; PROTEINS; PTEN; PTEN Phosphohydrolase - metabolism; STABILITY; TRANSCRIPTION; Degradation; PTEN; Stability; E-cadherin; Cell–cell adhesion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.08.154

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well-characterized tumor suppressor that negatively regulates cell growth and survival. Despite the critical role of PTEN in cell signaling, the mechanisms of its regulation are still under investigation. We reported here that PTEN expression could be controlled by overexpression or knock-down of E-cadherin in several mammary carcinoma cell lines. Furthermore, we showed that the accumulation of PTEN protein in E-cadherin overexpressing cells was due to increased PTEN protein stability rather than the regulation of its transcription. The proteasome-dependent PTEN degradation pathway was impaired after restoring E-cadherin expression. Moreover, maintenance of E-cadherin mediated cell–cell adhesion was necessary for its regulating PTEN. Altogether, our results suggested that E-cadherin mediated cell–cell adhesion was essential for preventing the proteasome degradation of PTEN, which might explain how breast carcinoma cells which lost cell–cell contact proliferate rapidly and are prone to metastasis.