Table 2.

Hallmarks of cancer and the IGF1 signaling pathway.

CANCER HALLMARK	IGF1 INVOLVEMENT
Sustained proliferative signaling	IGF1 stimulates proliferation and inhibits death in a variety of cell types. IGF1 functions as a progression factor required to traverse the cell cycle. IGF1 has an important role in stem cell biology.
Insensitivity to antigrowth signals	Cancer genes (e.g., tumor suppressors, oncogenes) adopt the IGF1 signaling pathway. Cellular and viral oncogenes require an intact IGF1 axis in order to elicit their transforming roles.
Evasion of apoptosis	The IGF1R exhibits a potent anti-apoptotic activity. IGF1R confers upon cells enhanced survivability. Cells deprived of the IGF1R do not undergo transformation.
Genome instability and mutation	p53, a DNA integrity sensor, suppresses IGF1R gene transcription. Mutation of p53 enhances IGF1R gene expression and IGF1-mediated mitogenesis. Activation of BRCA1 upon DNA damage leads to a reduction in IGF1R levels and IGF1 action.
Sustained angiogenesis	IGF1 enhances the hypoxic response by stabilizing HIF-α and upregulating VEGF-A. A functional cooperation between the IGF1R and VEGF pathways has been identified in cancer cells.
Tissue invasion and metastasis	Deregulated expression and availability of IGFs are regarded as key regulators of metastasis. Obesity leads to changes in the extracellular matrix and adipose cells, creating a cancer-permissive microenvironment.