AMPK-like proteins and their function in female reproduction and gynecologic cancer

Serine-threonine kinase (STK11), also known as liver kinase B1 (LKB1), is a regulator of cellular homeostasis through regulating the cellular ATP-to-ADP ratio. LKB1 is classified as a tumor suppressor and functions as the key activator of AMP-activated protein kinase (AMPK) and a family of serine-threonine kinases called AMPK-like proteins. These proteins include novel (nua) kinase family 1 (NUAK1 and 2), salt inducible kinase (SIK1), QIK (known as SIK2), QSK (known as SIK3 kinase), and maternal embryonic leuzine zipper kinase (MELK) on tightly controlled and specific residual sites. LKB1 also regulates brain selective kinases 1 and 2 (BRSK1 and 2), additional members of AMPK-like protein family, which functions are probably less studied. AMPK-like proteins play a role in variety of reproductive physiology functions such as follicular maturation, menopause, embryogenesis, oocyte maturation, and preimplantation development. In addition, dysfunctional activity of AMPK-like proteins contributes to apoptosis blockade in cancer cells and induction of the epithelial-mesenchymal transition required for metastasis. Dysregulation of these proteins occurs in ovarian, endometrial, and cervical cancers. AMPK-like proteins are still undergoing further classification and may represent novel targets for targeted gynecologic cancer therapies. In this chapter, we describe the AMPK-like family of proteins and their roles in reproductive physiology and gynecologic cancers.