Hyperglycemia-driven signaling bridges between diabetes and cancer.

Growing epidemiological evidence indicates an association between obesity, type 2 diabetes, and certain cancers, suggesting the existence of common underlying mechanisms in these diseases. Frequent hyperglycemias in type 2 diabetes promote pro-inflammatory responses and stimulate intracellular metabolic flux which rewires signaling pathways and influences the onset and advancement of different types of cancers. Here, we review the provocative impact of hyperglycemia on a subset of interconnected signalling pathways that regulate (i) cell growth and survival, (ii) metabolism adjustments, (iii) protein function modulation in response to nutrient availability (iv) and cell fate and proliferation and which are driven respectively by PI3K (Phosphoinositide 3-kinase), AMPK (AMP-activated protein kinase), O-GlcNAc (O-linked N-acetylglucosamine) and Wnt/β-catenin. Specifically, we will elaborate on their involvement in glucose metabolism, inflammation, and cell proliferation, highlighting their interplay in the pathogenesis of diabetes and cancer. Furthermore, the influence of antineoplastic and antidiabetic drugs on the unbridled cellular pathways will be examined. This review aims to inspire the next molecular studies to understand how type 2 diabetes may lead to certain cancers. This will contribute to personalized medicine and direct better prevention strategies.