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Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype
in vitro and malignant features in esophageal squamous cell carcinomas
#MMPMID27911865
Li Y
; Li X
; Kan Q
; Zhang M
; Li X
; Xu R
; Wang J
; Yu D
; Goscinski MA
; Wen JG
; Nesland JM
; Suo Z
Oncotarget
2017[Jan]; 8
(1
): 1058-1073
PMID27911865
show ga
Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this
study, we investigated the relationship between blocking mitochondrial pyruvate
carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as
aggressive features of esophageal squamous carcinoma. It was found that blocking
pyruvate transportation into mitochondria attenuated mitochondrial oxidative
phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg
effect. In addition, the HIF-1? expression and ROS production were also activated
upon UK5099 application. It was further revealed that the UK5099-treated cells
became significantly more resistant to chemotherapy and radiotherapy, and the
UK5099-treated tumor cells also exhibited stronger invasive capacity compared to
the parental cells. In contrast to esophageal squamous epithelium cells,
decreased MPC protein expression was observed in a series of 157 human squamous
cell carcinomas, and low/negative MPC1 expression predicted an unfavorable
clinical outcome. All these results together revealed the potential connection of
altered MPC expression/activity with the Warburg metabolic reprogramming and
tumor aggressiveness in cell lines and clinical samples. Collectively, our
findings highlighted a therapeutic strategy targeting Warburg reprogramming of
human esophageal squamous cell carcinomas.
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