DLAT subunit of the pyruvate dehydrogenase complex is upregulated in gastric cancer-implications in cancer therapy.
An iTRAQ-based tandem mass spectrometry approach was employed to relatively quantify proteins in the membrane proteome of eleven gastric cancer cell lines relative to a denominator non-cancer gastric epithelial cell line HFE145. Of the 882 proteins detected, 57 proteins were found to be upregulated with > 1.3-fold change in at least 6 of the 11 cell lines. Bioinformatics analysis revealed that these proteins are significantly associated with cancer, cell growth and proliferation, death, survival and cell movement. The catalogue of membrane proteins presented that are potential regulators/effectors of gastric cancer progression has implications in cancer therapy. DLAT, a subunit of the pyruvate dehydrogenase complex, was selected as a candidate protein for further studies as its function in gastric cancer has yet to be established. SiRNA studies supported a role of DLAT in gastric cancer cell proliferation and carbohydrate metabolism, reprogramming of which is a hallmark of cancer. Our study contributes to recent interest and discussion in cancer energetics and related phenomena such as the Warburg and Reverse Warburg effects. Future mechanistic studies should lead to the elucidation of the mode of action of DLAT in human gastric cancer and establish DLAT as a viable drug target.
Department of Biochemistry, Yong Loo Lin School of Medicine 117545, Singapore.
Wen Quan Jonathan
WQ
Goh
Bioinformatics Institute, Agency for Science and Technology 138671, Singapore.
Ghim Siong
GS
Ow
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore 117456, Singapore ; Bioinformatics Institute, Agency for Science and Technology 138671, Singapore ; School of Computing Engineering, Nanyang Technological University 639798, Singapore.
Vladimir A
VA
Kuznetsov
Department of Biochemistry, Yong Loo Lin School of Medicine 117545, Singapore.
Shirly
S
Chong
Department of Biochemistry, Yong Loo Lin School of Medicine 117545, Singapore ; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore 117456, Singapore ; Bioinformatics Institute, Agency for Science and Technology 138671, Singapore.
Yoon Pin
YP
Lim
DLAT; Gastric cancer; cancer energetics; membrane; proliferation; proteomics