The deregulation of Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase signaling constitutes a common event in colorectal cancers. However, the physiopathological functions of such a deregulation remains poorly understood. In the present study, we investigated the role of the deregulation of Met receptor in the neoplastic transformation of intestinal epithelial cells. To do so, the normal, well-established and characterized rat intestinal epithelial IEC-6 cells were transduced with a retrovirus carrying the oncogenic constitutive active form of Met receptor, Tpr-Met. Herein, we show that when compared to control IEC-6 cells, Tpr-Met-IEC-6 cells exhibit enhanced proliferation, loss of growth contact inhibition, cell morphological alterations, actin cytoskeletal reorganization, loss of E-cadherin expression and anchorage-independent growth. Moreover, Tpr-Met-IEC-6 cells are conferred the capacity to produce the pro-angiogenic factor vascular endothelial growth factor (VEGF) and to reduce the potent anti-angiogenic factor thrombospondin-1 (TSP-1). Of significance, Tpr-Met-IEC-6 cells are endowed with the ability to elicit angiogenic responses, and to form tumors and metastases in vivo. Hence, our study demonstrates for the first time that the sole oncogenic engagement of Met receptor in normal intestinal epithelial cells is sufficient to induce a wide array of cancerous biological processes that are fundamental to the initiation and malignant progression of colorectal cancers.
- Met receptor
- intestinal epithelial cells
- Copyright © 2009, American Journal of Physiology- Gastrointestinal and Liver Physiology