Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis
Open Access
- 23 July 2020
- Vol. 12 (8), 2014
- https://doi.org/10.3390/cancers12082014
Abstract
Src, originally identified as an oncogene, is a membrane-anchored tyrosine kinase and the Src family kinase (SFK) prototype. SFKs regulate the signalling induced by a wide range of cell surface receptors leading to epithelial cell growth and adhesion. In the intestine, the SFK members Src, Fyn and Yes regulate epithelial cell proliferation and migration during tissue regeneration and transformation, thus implicating conserved and specific functions. In patients with colon cancer, SFK activity is a marker of poor clinical prognosis and a potent driver of metastasis formation. These tumorigenic activities are linked to SFK capacity to promote the dissemination and tumour-initiating capacities of epithelial tumour cells. However, it is unclear how SFKs promote colon tumour formation and metastatic progression because SFK-encoding genes are unfrequently mutated in human cancer. Here, we review recent findings on SFK signalling during intestinal homeostasis, regeneration and tumorigenesis. We also describe the key nongenetic mechanisms underlying SFK tumour activities in colorectal cancer, and discuss how these mechanisms could be exploited in therapeutic strategies to target SFK signalling in metastatic colon cancer.Keywords
Funding Information
- Institut National Du Cancer (INCa-DGOS-Inserm 6045)
This publication has 150 references indexed in Scilit:
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif that is exploited by bacterial effectorsProceedings of the National Academy of Sciences of the United States of America, 2011
- Direct reprogramming of stem cell properties in colon cancer cells by CD44The EMBO Journal, 2011
- The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and functionNature Reviews Molecular Cell Biology, 2011
- Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximabOncogene, 2010
- Latent Bone Metastasis in Breast Cancer Tied to Src-Dependent Survival SignalsCancer Cell, 2009
- Cell growth, global phosphotyrosine elevation, and c-Met phosphorylation through Src family kinases in colorectal cancer cellsProceedings of the National Academy of Sciences of the United States of America, 2008
- Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitorsNature Biotechnology, 2007
- p140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase activityThe EMBO Journal, 2007
- Src kinase phosphorylates Caspase-8 on Tyr380: a novel mechanism of apoptosis suppressionThe EMBO Journal, 2006