Beta1 integrin modulates the anchorage independent growth, invasion and migration of prostate cancer cell line PC3

Abstract

Integrins provide mechanical continuity between the extra- and intracellular environments. Upon binding to extracellular matrix (ECM), integrins interact with downstream effectors to promote cell adhesion, proliferation and migration. In contrast to its well-known role in adhesion, we have found that beta 1 integrin is also involved in the anchorage independent (AI) growth of prostate tumor cells. In concurrence with our previous findings, stable depletion of beta1 integrin in PC3 cells using an shRNA approach resulted in the complete inability of cells to form colonies in soft agarose, while adherent monolayer growth remained unaffected. In order to address the mechanism for beta1 integrin dependent AI growth, we examined the expression and localization of beta-catenin and E-cadherin, both of which are known to modulate AI growth. Migration and invasion through matrigel were found to be impeded by depletion of beta1 integrin. A qPCR array identified potential downstream targets that could be altered as a result of beta1 integrin depletion, these were further examined in all cell lines and it was found that TGFbeta1 is reduced in shITGB1 expressing cells. Taken together, these findings suggest a role for both beta1 integrin in driving anchorage independent growth and invasion of cancer cells.