Endocrine-related cancers and the role of AMPK

AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis involved in the regulation of a number of physiological processes including β-oxidation of fatty acids, lipogenesis, protein and cholesterol synthesis, as well as cell cycle inhibition and apoptosis. Important changes to these processes are known to occur in cancer due to changes in AMPK activity within cancer cells and in the periphery. This review aims to present findings relating to the role and regulation of AMPK in endocrine-related cancers. Obesity is a known risk factor for many types of cancers and a number of endocrine factors, including adipokines and steroid hormones, are regulated by and regulate AMPK. A clear role for AMPK in breast cancer is evident from the already impressive body of work published to date. However, information pertaining to its role in prostate cancer is still contentious, and future work should unravel the intricacies behind its role to inhibit, in some cases, and stimulate cancer growth in others. This review also presents data relating to the role of AMPK in cancers of the endometrium, ovary and colon, and discusses the possible use of AMPK-activating drugs including metformin for the treatment of all endocrine-related cancers.

► AMPK has an emerging role in the regulation of endocrine-related cancer cell growth.
► In most cases, AMPK is a negative regulator of cancer cell proliferation.
► AMPK inhibits cell growth by stimulating p53 and inhibiting mTOR.
► AMPK inhibits PGE2 and estrogen biosynthesis, key mediators of cell proliferation.
► AMPK-activating drugs decrease tumour cell growth and induce apoptosis.