Metformin: A New Inhibitor of the Wnt Signaling Pathway in Cancer
Domenico Conza,
Paola Mirra,
Francesca Fiory,
Luigi Insabato,
Antonella Nicolò,
Francesco Beguinot,
Luca Ulianich
Affiliations
Domenico Conza
URT Genomics of Diabetes, Institute of Endocrinology and Experimental Oncology, National Research Council & Department of Translational Medicine, University of Naples “Federico II”, 80131 Naples, Italy
Paola Mirra
URT Genomics of Diabetes, Institute of Endocrinology and Experimental Oncology, National Research Council & Department of Translational Medicine, University of Naples “Federico II”, 80131 Naples, Italy
Francesca Fiory
URT Genomics of Diabetes, Institute of Endocrinology and Experimental Oncology, National Research Council & Department of Translational Medicine, University of Naples “Federico II”, 80131 Naples, Italy
Luigi Insabato
Department of Advanced Biomedical Sciences, University of Naples “Federico II”, 80131 Naples, Italy
Antonella Nicolò
URT Genomics of Diabetes, Institute of Endocrinology and Experimental Oncology, National Research Council & Department of Translational Medicine, University of Naples “Federico II”, 80131 Naples, Italy
Francesco Beguinot
URT Genomics of Diabetes, Institute of Endocrinology and Experimental Oncology, National Research Council & Department of Translational Medicine, University of Naples “Federico II”, 80131 Naples, Italy
Luca Ulianich
URT Genomics of Diabetes, Institute of Endocrinology and Experimental Oncology, National Research Council & Department of Translational Medicine, University of Naples “Federico II”, 80131 Naples, Italy
The biguanide drug metformin is widely used in type 2 diabetes mellitus therapy, due to its ability to decrease serum glucose levels, mainly by reducing hepatic gluconeogenesis and glycogenolysis. A considerable number of studies have shown that metformin, besides its antidiabetic action, can improve other disease states, such as polycystic ovary disease, acute kidney injury, neurological disorders, cognitive impairment and renal damage. In addition, metformin is well known to suppress the growth and progression of different types of cancer cells both in vitro and in vivo. Accordingly, several epidemiological studies suggest that metformin is capable of lowering cancer risk and reducing the rate of cancer deaths among diabetic patients. The antitumoral effects of metformin have been proposed to be mainly mediated by the activation of the AMP-activated protein kinase (AMPK). However, a number of signaling pathways, both dependent and independent of AMPK activation, have been reported to be involved in metformin antitumoral action. Among these, the Wingless and Int signaling pathway have recently been included. Here, we will focus our attention on the main molecular mechanisms involved.
