Dissecting Oncogenic RTK Pathways in Colorectal Cancer Initiation and Progression.

Colorectal cancer (CRC) is a progressive disorder associated with an accumulation of multiple heterogeneous genetic alterations in intestinal epithelial cells (IEC). However, when these cells undergo neoplastic transformation and become cancerous and metastatic, they invariably acquire hallmarks conferring them the ability to hyperproliferate, escape growth-inhibitory and death-inducing cues, and promote angiogenesis as well as epithelial-to-mesenchymal transformation (EMT), fostering their invasive dissemination from primary tumor into distant tissues. Compelling clinical and experimental evidence suggest that aberrant engagement of cell surface growth factor receptor tyrosine kinase (RTK) signaling, like that of the hepatocyte growth factor (HGF)/MET receptor, underlies CRC metastatic progression by promoting these cancer hallmarks.

Tumour-promoting role of SOCS1 in colorectal cancer cells.

The SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of p53 tumour suppressor activity.

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

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 remain poorly understood. In the present study, we investigated the role of the deregulation of Met receptor in the neoplastic transformation of intestinal epithelial cells.