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Dissecting Oncogenic RTK Pathways in Colorectal Cancer Initiation and Progression.
- Source :
-
Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2018; Vol. 1765, pp. 27-42. - Publication Year :
- 2018
-
Abstract
- 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. To date, though, the use of RTK-targeting agents has been viewed as a promising approach for the treatment of metastatic CRC, clinical success has been modest.Our vision is that the prospect of designing RTK-based, improved and innovative CRC therapies and prognostic markers likely rests on a comprehensive understanding of the biological processes and underlying regulatory molecular mechanisms by which deregulation of RTK signaling governs IEC's neoplastic transformation and their transition from noninvasive to metastatic and malignant cells. Herein, we describe our scheme for defining the full scope of oncogenic MET-driven cancer biological processes, in cellulo and in vivo, as well as the individual contribution of MET-binding effectors in a nontransformed IEC model, the IEC-6 cell line.
- Subjects :
- Animals
Cell Line, Tumor
Disease Models, Animal
Disease Progression
Epithelial Cells pathology
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
Intestinal Mucosa cytology
Intestinal Mucosa pathology
Liver Neoplasms pathology
Lung Neoplasms pathology
Mice
Mice, Nude
Rats
Signal Transduction
Cell Transformation, Neoplastic pathology
Colorectal Neoplasms pathology
Liver Neoplasms secondary
Lung Neoplasms secondary
Proto-Oncogene Proteins c-met metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6029
- Volume :
- 1765
- Database :
- MEDLINE
- Journal :
- Methods in molecular biology (Clifton, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 29589299
- Full Text :
- https://doi.org/10.1007/978-1-4939-7765-9_2