BCKDK of BCAA Catabolism Cross-talking With the MAPK Pathway Promotes Tumorigenesis of Colorectal Cancer

EBioMedicine
Peipei XueFeng Zhu

Abstract

Branched-chain amino acids catabolism plays an important role in human cancers. Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females, and the new global incidence is over 1.2 million cases. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) is a rate-limiting enzyme in branched-chain amino acids catabolism, which plays an important role in many serious human diseases. Here we investigated that abnormal branched-chain amino acids catabolism in colorectal cancer is a result of the disease process, with no role in disease initiation; BCKDK is widely expressed in colorectal cancer patients, and those patients that express higher levels of BCKDK have shorter survival times than those with lower levels; BCKDK promotes cell transformation or colorectal cancer ex vivo or in vivo. Mechanistically, BCKDK promotes colorectal cancer by enhancing the MAPK signaling pathway through direct MEK phosphorylation, rather than by branched-chain amino acids catabolism. And the process above could be inhibited by a BCKDK inhibitor, phenyl butyrate.

Citations

May 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dipsikha BiswasThomas Pulinilkunnil
Oct 26, 2018·Hypertension·Zhen-Yu ZhangJan A Staessen
Dec 1, 2019·Experimental & Molecular Medicine·Ji Hyeon LeeJaekyoung Son
Jun 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jessica CannavinoEric N Olson
Aug 7, 2021·Frontiers in Physiology·Gagandeep MannOlasunkanmi A J Adegoke

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BETA
transfection
immunoprecipitation
Xenografts
Assay
xenograft
co-immunoprecipitation

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