Laminin-10 and Its Receptors in Breast Carcinoma: Cooperation of Alpha 6 Beta 4 and Alpha 3 Beta 1 Integrin Receptors in Breast Carcinoma Invasion

摘要

Alpha 6 beta 4 integrin activates PI3-K, which facilitates breast carcinoma cell migration and invasion. In this report we characterize one more pathway acting downstream of alpha 6 beta 4/PI3-K. We show that RhoA activation is needed as an initial signal for induction of lamellae, but PI3-K dependent activation of PKC epsilon is needed for stabilization of lamellae and hence for efficient carcinoma cell migration and invasion. PKC epsilon is constitutively active in carcinoma cells, and provides a separate, parallel signal that acts independently of RhoA activity. RhoA activation is an absolute requirement for initial steps of lamellae formation, but efficient cell motility and invasion requires PKC epsilon activity. Other PKC isoforms cannot replace PKC epsilon, and therefore PKC epsilon provides a promising target for pharmacological treatments and gene therapy of breast cancer.