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The Role of Pyruvate Kinase Isoform M1/2 in Colorectal Cancer
Author(s) -
Park Bohye,
Kim Ji Yeon,
Crumbley Christopher,
Wirthwein Kaci,
Riffey Olivia,
Beaird Jacob,
Smith Mary,
Donohoe Dallas
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03170
Subject(s) - pkm2 , butyrate , pyruvate kinase , anaerobic glycolysis , warburg effect , cancer research , glycolysis , colorectal cancer , pyruvate dehydrogenase kinase , chemistry , cancer , biochemistry , biology , pyruvate dehydrogenase complex , medicine , metabolism , enzyme , fermentation
Colorectal cancer cell (CRC) increases the utilization of glucose and decreases the oxidation of butyrate, which is a primary energy source for non‐cancerous colonocytes. Butyrate is a short‐chain fatty acid that is a bacterial‐derived fiber fermentation product. It takes years for the colorectal adenoma to manifest as it progresses toward invasive carcinoma. Within this timeframe, the adenoma must acquire key genomic and metabolic modifications that promote tumor growth and progression. Understanding the metabolic shift mechanisms away from butyrate oxidation to glycolysis in the CRC is significant. The overexpression of the pyruvate kinase isoform M2 (PKM2) is observed in biopsies of colorectal cancer patients, which is a hallmark of cancer. Pyruvate kinase is a metabolic enzyme that catalyzes the last step in glycolysis, which converts phosphoenolpyruvate to pyruvate generating ATP. PKM1 is generally expressed in adult differentiated tissues, such as normal non‐cancerous colonic tissue, where it promotes oxidative metabolism. In contrast, PKM2 is expressed in proliferating cells, including colorectal cancer cells, where it enhances aerobic glycolysis. However, the function of PKM2 in colorectal cancer tumorigenesis remains controversial. Our preliminary studies suggest that PKM2 drives colorectal metabolism away from butyrate and toward glucose utilization. A stable knockdown of PKM2 in colorectal cancer cells increased the oxidation of butyrate. The major hypothesis for this project is that through enhancing glucose utilization and suppressing butyrate, utilization PKM2 promotes colorectal tumor progression. Here, we demonstrate that, when expressed rather than PKM2, the PKM1 increases butyrate oxidation in cancerous colonocytes. Support or Funding Information USDA R011770176