IGF-I mediated survival pathways in normal and malignant cells

Area of Science:

• Cell Biology
• Molecular Biology
• Endocrinology

Background:

• Insulin-like growth factors (IGFs) are recognized as critical regulators of cell survival and proliferation.
• IGFs offer trophic support to diverse cell types and organ cultures, delaying apoptosis through intrinsic and extrinsic pathways.
• IGFs can also prevent necrosis and autophagy, highlighting their broad cytoprotective functions.

Purpose of the Study:

• To elucidate the role of IGFs and their signaling pathways in promoting cell survival under stress.
• To explore the context-specific effects of IGFs on cell viability based on cell origin and stress type.
• To review the association of dysregulated IGF signaling with human diseases, including cancers and organ pathologies.

Main Methods:

• Review of in vitro studies on IGFs' effects on cell death pathways (apoptosis, necrosis, autophagy).
• Analysis of literature linking IGF signaling to tissue-specific stress responses.
• Examination of the role of IGF dysregulation in various human diseases and childhood cancers.

Main Results:

• IGFs significantly delay programmed cell death (apoptosis) via mitochondrial and death receptor pathways.
• IGF-mediated cell survival is dependent on cell type and the nature of cellular stress.
• Dysregulated IGF signaling is strongly associated with human cancers, acute renal failure, brain injury, and cardiac disease.

Conclusions:

• IGFs are potent survival factors whose effects are highly context-dependent.
• Understanding IGF signaling pathways is crucial for developing therapeutic strategies for diseases involving cellular stress and death.
• Aberrant IGF signaling contributes to the pathogenesis of numerous human conditions, underscoring its clinical relevance.