Src phosphorylates Tyr284 in TGF-beta type II receptor and regulates TGF-beta stimulation of p38 MAPK during breast cancer cell proliferation and invasion.

Genetic and epigenetic events often negate the cytostatic function of transforming growth factor-beta (TGF-beta) in mammary epithelial cells (MEC), which ultimately enables malignant MECs to proliferate, invade, and metastasize when stimulated by TGF-beta. The molecular mechanisms underlying this phenotypic conversion of TGF-beta function during mammary tumorigenesis remain poorly defined. We previously established alpha(v)beta(3) integrin and Src as essential mediators of mitogen-activated protein kinase (MAPK) activation, invasion, and epithelial-to-mesenchymal transition stimulated by TGF-beta in normal and malignant MECs.

Role of transforming growth factor-beta in cancer progression.

Invasion and metastasis are the most lethal characteristics of cancer and the leading causes of cancer-related death. Transforming growth factor (TGF)-beta is a multifunctional cytokine that normally functions to prevent the uncontrolled proliferation of epithelial, endothelial and hematopoietic cells. Quite dichotomously, however, aberrant genetic or epigenetic events often negate the cytostatic function of TGF-beta in these cells, leading to tumor formation.

Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial-mesenchymal transition in mammary epithelial cells.

Introduction: Transforming growth factor (TGF)-beta suppresses breast cancer formation by preventing cell cycle progression in mammary epithelial cells (MECs). During the course of mammary tumorigenesis, genetic and epigenetic changes negate the cytostatic actions of TGF-beta, thus enabling TGF-beta to promote the acquisition and development of metastatic phenotypes. The molecular mechanisms underlying this conversion of TGF-beta function remain poorly understood but may involve signaling inputs from integrins.