Novel function of biguanides in inhibition of phospholipase D1 expression via a translational mechanism in cancer cells

Phospholipase D(PLD)and its product phosphatidic acid(PA)function as pleiotropic factors in the regulation of cancer progression,which includes the promotion of cell growth,survival,cell migration,and angiogenesis.1 Chem-ical inhibition of the enzymatic activity of PLD1 and PLD2,or genetic down-regulation of their expression both induce tumor suppression,1 while the compounds for PLD expres-sion inhibition are barely reported.Here,we astonishingly found that the anti-hyperglycemic agents biguanides decreased PLD1 protein expression in cancer cells and further investigated its underlying regulatory mechanism.