Oncogenic engagement of the Met receptor is sufficient to evoke angiogenic, tumorigenic, and metastatic activities in rat intestinal epithelial cells

摘要: The deregulation of Met/hepatocyte growth factor (HGF) receptor tyrosine kinase signaling constitutes a common event in colorectal cancers. However, the physiopathological functions such remain poorly understood. In present study, we investigated role Met neoplastic transformation intestinal epithelial cells. To do so, normal, well-established and characterized rat IEC-6 cells were transduced with retrovirus carrying oncogenic constitutive active form receptor, Tpr-Met. Herein, show that compared control cells, Tpr-Met-IEC-6 exhibit enhanced proliferation, loss growth-contact inhibition, cell morphological alterations, actin cytoskeletal reorganization, E-cadherin expression anchorage-independent growth. Moreover, are conferred capacity to produce proangiogenic VEGF reduce potent antiangiogenic thrombospondin-1. Of significance, endowed ability elicit angiogenic responses tumors metastases vivo. Hence, our study demonstrates for first time sole engagement normal is sufficient induce wide array cancerous biological processes fundamental initiation malignant progression