From these data, we can argue that activated insulin receptor plays a fundamental role at the early stages of tumorigenesis, where late stages could be characterized by a shift toward more active oncogenic drivers.
Insulin, insulinlike growth factor 1, and insulinlike growth factor 2 signaling through the insulin receptor and the insulinlike growth factor 1 receptor can induce tumorigenesis, accounting to some extent for the link between diabetes, obesity, and cancer.
Insulin-like growth factor (IGF) signaling through human insulin receptor isoform A (IR-A) contributes to tumorigenesis and intrinsic resistance to anti-IGF1R therapy.
Our findings support this hypothesis and suggest that in affected individuals, hyperactivation of the AP-2 gene through the overexpression of IR may play a key role in breast carcinogenesis.
This gene shares structural and sequence homologies with the epidermal growth factor receptor (erb-B oncogene) and members of the src family of oncogenes, suggesting that alterations in the insulin receptor, resulting from chromosomal translocation, could lead to a role in tumorigenesis.
Thus, our current data demonstrate that both INSR and IGF1R are directly targeted by C-myc and exert similar effects to promote the tumorigenesis and metastasis of TSCC through the NF-κB pathway.
While most insulin analogues primarily activated the INSR, the mitogenic activation pattern of glargine was highly similar to IGF1 and insulin AspB10, known to bind IGF1R and induce carcinogenesis.