title: Restoring E-cadherin-mediated cell-cell adhesion increases PTEN protein level and stability in human breast carcinoma cells.
abstract: 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.
authors.affiliation: Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
authors.forename: Zengxia
authors.initials: Z
authors.lastname: Li
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Fu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhao
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.forename: Bram Peter
authors.initials: BP
authors.lastname: Prins
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004795:Enzyme Stability; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human