Abstract
Insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation. Upregulation of the IGF1R pathway constitutes a common paradigm shared with other receptor tyrosine kinases such as EGFR, HER2, and MET in different cancer types, including colon cancer. The main IGF1R signaling pathways are PI3K-AKT and MAPK-MEK. However, different processes, such as post-translational modification (SUMOylation), epithelial-to-mesenchymal transition (EMT), and microenvironment complexity, can also contribute to intrinsic and acquired resistance. Here, we discuss new strategies for adequate drug development in metastatic colorectal cancer patients.
Highlights
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Insulin and insulin-like growth factor 1 (IGF1) are closely related ligands that interact with the insulin receptor (INSR) and IGF1 receptor (IGF1R) family of receptors
IGF1R is closely related to INSR, with sequence similarity varying from 41% to 84%, depending on the domain
Summary
Insulin and insulin-like growth factor 1 (IGF1) are closely related ligands that interact with the insulin receptor (INSR) and IGF1 receptor (IGF1R) family of receptors. Other relevant aspects related to IGF1R signaling involve interactions with other oncogenic tyrosine kinase receptors and mutations in downstream pathways, such as PI3K/AKT and RAS/MAPK [29]. The interaction between ubiquitylation and SUMOylation is complex and SUMO and ubiquitin are often conjugated to the same substrate, lysine, acting antagonistically or sequentially [36]. Another post-translational modification that was recently identified as a SUMO regulator is acetylation. IGF1R exhibits a different function when phosphorylated in the nucleus because it acts as a transcription regulator (instead of a tyrosine kinase receptor) and its nuclear location is associated with poor prognosis [45]. Sci. 2021, 22, 5019 a monoclonal antibody, or AEV-541, a tyrosine kinase inhibitor) promoted IGF1R nuclear internalization and PIAS3 inhibition decreased cytoplasm–nuclear IGF1R trafficking [47]
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