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Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer
- Source :
- Biomolecules, Vol 10, Iss 12, p 1617 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in cancerous cells. This latter finding has been shown to associate with both a relative and absolute increase in IR isoform-A (IR-A) expression, missing 12 aa in its EC subunit corresponding to exon 11. Since IR-A is a high-affinity transducer of Insulin-like Growth Factor-II (IGF-II) signals, a growth factor is often secreted by cancer cells; such event offers a direct molecular link between IR-A/IR-B increased ratio in insulin resistance states (obesity and type 2 diabetes) and the malignant advantage provided by IGF-II to solid tumors. Nonetheless, recent findings on the biological role of isoforms for cellular signaling components suggest that the preferential expression of IR isoform-A may be part of a wider contextual isoform-expression switch in downstream regulatory factors, potentially enhancing IR-dependent oncogenic effects. The present review focuses on the role of isoform- and paralog-dependent variability in the IR and downstream cellular components playing a potential role in the modulation of the IR-A signaling related to the changes induced by insulin-resistance-linked conditions as well as to their relationship with the benign versus malignant transition in underlying solid tumors.
- Subjects :
- IR: insulin receptor
IGF: insulin-like growth factor
HIF: hypoxia-inducible factor
Isoform: for the scope of this review, the term isoform is restricted to products of alternatively spliced coding genes
Paralog: the product of gene variants with high sequence similarity encoded by duplicated genes in the genome
MAPK-ERK: Mitogen-activated protein Kinase-Extracellular-signal-regulated Kinase
Microbiology
QR1-502
Subjects
Details
- Language :
- English
- ISSN :
- 10121617 and 2218273X
- Volume :
- 10
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.37706b4388a6470081611b4772020034
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/biom10121617