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.
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.
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.
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.