Tumor pyruvate kinase M2: A promising molecular target of gastrointestinal cancer

Abstract

Gastrointestinal (GI) cancer is one of the most common causes of cancer-related deaths worldwide. Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy. Pyruvate kinase isoform M2 (PKM2), a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate (PEP) to pyruvate, confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment. In this review, we have summarized current research on the expression and regulation of PKM2 in tumor cells, and its potential role in GI carcinogenesis and progression. Furthermore, we have also discussed the potential of PKM2 as a diagnostic and screening marker, and a therapeutic target in GI cancer.

Keywords: PKM2 (pyruvate kinase M2); gastrointestinal cancer; gene transcription; metabolic reprogramming; therapy targets.

1

Regulation of different pyruvate kinase (PK) isoforms in mammalian cells. There are 4 isozymes of PK in mammals: L, R, M1 and M2. L and R isoforms of PK originate from PKLR gene and M1 and M2 isoforms of PK are alternatively spliced forms of the PKM gene. L type is major isozyme in the liver, R is found in red cells, M1 is the main form in muscle, heart and brain, and M2 is found in early fecal tissues.