Abstract
Tyrosine kinases (TKs) phosphorylate proteins on tyrosine residues as an intracellular signalling mechanism to coordinate intestinal epithelial cell communication and fate decision. Deregulation of their activity is ultimately connected with carcinogenesis. In colorectal cancer (CRC), it is still unclear how aberrant TK activities contribute to tumour formation because TK-encoding genes are not frequently mutated in this cancer. In vertebrates, several TKs are under the control of small adaptor proteins with potential important physiopathological roles. For instance, they can exert tumour suppressor functions in human cancer by targeting several components of the oncogenic TK signalling cascades. Here, we review how the Src-like adaptor protein (SLAP) and the suppressor of cytokine signalling (SOCS) adaptor proteins regulate the SRC and the Janus kinase (JAK) oncogenic pathways, respectively, and how their loss of function in the intestinal epithelium may influence tumour formation. We also discuss the potential therapeutic value of these adaptors in CRC.
Highlights
Tyrosine kinases (TKs) phosphorylate proteins on tyrosine residues as an intracellular signalling mechanism to coordinate intestinal epithelial cell communication and fate decision
Among the various oncogenic pathways, the tyrosine kinase (TK) signalling cascades have emerged as important determinants of metastasis development
Mitogen-activated protein kinase (MAPK) signalling is mainly induced in CMS1 and 3 and receptor TKs (RTKs) signalling in CMS2
Summary
Colorectal cancer (CRC) is one of the leading causes of malignancy-related death worldwide. Among the various oncogenic pathways, the tyrosine kinase (TK) signalling cascades have emerged as important determinants of metastasis development Consistent with this idea, therapies to target the receptor TKs (RTKs) epidermal growth factor receptor (EGFR) or vascular endothelial growth factor receptor (VEGFR) have been developed for metastatic CRC and are currently used in the clinic [4]. They prolong patient survival only by several months and many patients with CRC, including those with cancer displaying dysregulated RAS signalling, do not respond to anti-EGFR therapies [5]. It should be noticed that this classification represents more than 80% of the analysed CRC tumours and the others could represent mixed phenotypes
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