PTPmu Regulates Cell Adhesion and Signaling in Human Prostate Cancer Cells.

摘要

We are investigating how cell adhesion-induced signals are transduced to negatively regulate cell growth and how it is altered in prostate cancer. Extracellular events that regulate cell growth are transmitted by changes in tyrosine phosphorylation, which is controlled by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Cancer causing genes encode PTKs that cause uncontrolled cell growth suggesting that PTPs play a role in negative growth regulation. Both cell adhesion molecules and tyrosine phosphorylation regulate contact inhibition of growth. Prostate cancer cells have defects in cell adhesion and contact inhibition. The receptor PTP, PTPmicron, directly interacts with E-cadherin, the cell-cell adhesion molecule in prostate cells. Loss of components of the cadherin pathway has been observed in prostate cancer cells. We recently demonstrated that PTPmicron is no longer expressed in prostate cancer cells. Re-expression of PTPmicron restores adhesion mediated by PTPp, E-cadherin and N-cadherin as well as negatively regulates cell growth. A detailed analysis of how PTPmicron alters adhesion, cell growth and signal transduction is described and provides insights into both normal cell growth as well as malignant transformation in prostate cancer. Our results indicate that PTPmicron is required for norma prostate cell adhesion and its loss plays a role in cancer progression.