Deciphering the dual role and prognostic potential of PINK1 across cancer types.

Abstract

Metabolic rewiring and deregulation of the cell cycle are hallmarks shared by many cancers. Concerted mutations in key tumor suppressor genes, such as PTEN, and oncogenes predispose cancer cells for marked utilization of resources to fuel accelerated cell proliferation and chemotherapeutic resistance. Mounting research has demonstrated that PTEN-induced putative kinase 1 (PINK1) acts as a pivotal regulator of mitochondrial homeostasis in several cancer types, a function that also extends to the regulation of tumor cell proliferative capacity. In addition, involvement of PINK1 in modulating inflammatory responses has been highlighted by recent studies, further expounding PINK1’s multifunctional nature. This review discusses the oncogenic roles of PINK1 in multiple tumor cell types, with an emphasis on maintenance of mitochondrial homeostasis, while also evaluating literature suggesting a dual oncolytic mechanism based on PINK1’s modulation of the Warburg effect. From a clinical standpoint, its expression may also dictate the response to genotoxic stressors commonly used to treat multiple malignancies. By detailing the evidence suggesting that PINK1 possesses distinct prognostic value in the clinical setting and reviewing the duality of PINK1 function in a context-dependent manner, we present avenues for future studies of this dynamic protein.