Chronic insulin exposure induces EMT-associated changes and increases migration and invasion in cancer cells

Abstract

Metastasis significantly worsens cancer prognosis and survival, and epidemiological studies suggest that metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) may be associated with poorer cancer outcomes. Recent studies emphasize changes in the tumor microenvironment (TME), including angiogenesis and epithelial-to-mesenchymal transition (EMT); however, early detection of metastasis and identification of high-risk TME factors remain challenging. Because insulin is elevated in hyperinsulinemic states and can influence growth-related signalling pathways, we investigated whether chronic insulin exposure promotes EMT-associated and invasion-associated changes using SKOV3 ovarian cancer cells as an in vitro model. Insulin exposure was associated with altered expression of EMT-related genes, changes in epithelial and mesenchymal markers, and increased migration and invasion in vitro. Supportive RT-qPCR analyzes in A549 and MDA-MB-231 cells showed similar insulin-associated changes in selected transcriptional markers, providing valuable insights into the role of insulin in cancer metastasis, potentially opening an avenue for further exploration of the connection between T2DM and metastatic progression in a broader range of tumors and in vivo models.