Pyruvate kinase M2: A multifarious enzyme in non-canonical localization to promote cancer progression

Publication date: April 2019Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2Author(s): Sajid Amin, Peng Yang, Zhuoyu LiAbstractRewiring glucose metabolism, termed as Warburg effect or aerobic glycolysis, is a common signature of cancer cells to meet their high energetic and biosynthetic demands of rapid growth and proliferation. Pyruvate kinase M2 isoform (PKM2) is a key player in such metabolic reshuffle, which functions as a rate-limiting glycolytic enzyme in the cytosol of highly-proliferative cancer cells. During the recent decades, PKM2 has been extensively studied in non-canonical localizations such as nucleus, mitochondria, and extracellular secretion, and pertained to novel biological functions in tumor progression. Such functions of PKM2 open a new avenue for cancer researchers. This review summarizes up-to-date functions of PKM2 at various subcellular localizations of cancer cells and draws attention to the translocation of PKM2 from cytosol into the nucleus induced by posttranslational modifications. Moreover, PKM2 in tumor cells could have an important role in resistance acquisition processes against various chemotherapeutic drugs, which have raised a concern on PKM2 as a potential therapeutic target. Finally, we summarize the current status and future perspectives to improve the potential of PKM2 as a therapeutic target for the development of anticancer therapeutic strategies.
Source: Biochimica et Biophysica Acta (BBA) Reviews on Cancer - Category: Cancer & Oncology Source Type: research