Insulin-Like Growth Factor Modulation in Cancer and Muscle Systems

The insulin-like growth factor (IGF) axis exerts a central role in coordinating cellular growth, survival and differentiation across diverse tissues. IGF-1, produced as multiple prohormone isoforms via alternative splicing, interacts with its primary receptor (IGF-1R) and is modulated by a family of binding proteins (IGFBPs). In muscle tissue, finely tuned IGF-1 signalling drives satellite‐cell activation, myofibre hypertrophy and regeneration through both endocrine and local autocrine mechanisms. In contrast, aberrant IGF-1 axis activation in cancer fosters tumour cell proliferation, resistance to apoptosis and metastatic behaviour. Differential expression of IGF-1 splice variants and their bioactive E-peptides further refines this repertoire of effects, with some isoforms displaying receptor-independent actions. Crosstalk with inflammatory cytokines, nutrient sensors and proprotein convertases integrates systemic and microenvironmental cues to regulate IGF-1 production, processing and bioavailability. Collectively, modulation of the IGF axis bridges physiological tissue maintenance and pathological proliferation, highlighting its global significance as both a therapeutic target in oncology and a facilitator of muscle repair and performance.

Research from Nature Portfolio

Recent studies have illuminated the role of proIGF-1 E-domains as intrinsically disordered regions that govern prohormone stability, maturation and subcellular trafficking. A conserved glycosylation motif within the Ea-domain was shown to protect proIGF-1 from proteasomal degradation, thereby sustaining mature IGF-1 production under varying nutrient conditions. Inhibitors of glycosylation selectively diminished Ea-domain-dependent secretion without affecting other isoforms, while alternative E-domains directed distinct nuclear or cytoplasmic localisation patterns. These insights detail how post-translational modification of IGF-1 precursors fine-tunes ligand availability and spatial signalling in both normal physiology and disease states.

Insulin-Like Growth Factor Modulation in Cancer and Muscle Systems publication trend

The graph below shows the total number of articles in insulin-like growth factor modulation in cancer and muscle systems across all publications each year (not limited to Nature Index journals).

Technical terms

Insulin-Like Growth Factor-1 (IGF-1): A peptide hormone that promotes cell growth, survival and differentiation.

IGF-1 Receptor (IGF-1R): A cell-surface tyrosine kinase that mediates IGF-1 signalling upon ligand binding.

Insulin-Like Growth Factor Binding Proteins (IGFBPs): A family of proteins that bind IGF-1 with high affinity, modulating its bioavailability and activity.

Alternative Splicing: The process by which different combinations of exons are joined to generate multiple mRNA transcripts from a single gene.

Isoform: A variant of a protein arising from alternative transcription, splicing or post-translational modification.

E-Domain: The carboxy-terminal extension of proIGF-1 precursors that influences stability, localisation and secretion.

References

1. The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity. Molecular Medicine (2014).
2. Insulin-Like Growth Factor-1 (IGF-1) and Its Monitoring in Medical Diagnostic and in Sports. Biomolecules (2021).
3. Role of Alternatively Spliced Messenger RNA (mRNA) Isoforms of the Insulin-Like Growth Factor 1 (IGF1) in Selected Human Tumors. International Journal of Molecular Sciences (2020).
4. The intrinsically disordered E-domains regulate the IGF-1 prohormones stability, subcellular localisation and secretion. Scientific Reports (2018).
5. Processing of Wild-type and Mutant Proinsulin-like Growth Factor-IA by Subtilisin-related Proprotein Convertases*. Journal of Biological Chemistry (1997).