Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer

研究成果: Article

64 引文 (Scopus)

摘要

The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and is associated with tumor malignancy. Pyruvate dehydrogenase kinase-1 (PDK1) and PDK3 participate in the metabolic switch of cancer cells; however, the medical significance of PDK1 and PDK3 in cancer progression is not known. Here, we assessed the expression profiles of PDK1 and PDK3 in colorectal cancer. Western blot analysis (n = 74) demonstrated that PDK3 was markedly increased in colon cancer compared to that in adjacent normal tissues, whereas PDK1 was decreased in cancer cells. In addition, PDK3 expression was positively correlated with that of hypoxia inducible factor-1α (HIF-1α) in cancer cells. Further analysis using immunohistochemical staining revealed that PDK3 levels were positively associated with severity of cancer and negatively associated with disease-free survival. In vitro studies using several colon cancer cell lines showed that PDK3 expression was controlled by HIF-1α and contributed to hypoxia-induced increased drug resistance, perhaps explaining why patients with PDK3 overexpression have a greater incidence of treatment failure. Taken together, our findings suggest that PDK3 plays an important role in the metabolic switch and drug resistance of colon cancer and is potentially a novel target for cancer therapy.

原文English
頁(從 - 到)1405-1414
頁數10
期刊American Journal of Pathology
179
發行號3
DOIs
出版狀態Published - 2011 九月 1

指紋

Drug Resistance
Colonic Neoplasms
Recurrence
Neoplasms
Hypoxia-Inducible Factor 1
pyruvate dehydrogenase (acetyl-transferring) kinase
Glycolysis
Treatment Failure
Disease-Free Survival
Colorectal Neoplasms
Respiration
Western Blotting
Staining and Labeling
Cell Line
Incidence

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

引用此文

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title = "Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer",
abstract = "The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and is associated with tumor malignancy. Pyruvate dehydrogenase kinase-1 (PDK1) and PDK3 participate in the metabolic switch of cancer cells; however, the medical significance of PDK1 and PDK3 in cancer progression is not known. Here, we assessed the expression profiles of PDK1 and PDK3 in colorectal cancer. Western blot analysis (n = 74) demonstrated that PDK3 was markedly increased in colon cancer compared to that in adjacent normal tissues, whereas PDK1 was decreased in cancer cells. In addition, PDK3 expression was positively correlated with that of hypoxia inducible factor-1α (HIF-1α) in cancer cells. Further analysis using immunohistochemical staining revealed that PDK3 levels were positively associated with severity of cancer and negatively associated with disease-free survival. In vitro studies using several colon cancer cell lines showed that PDK3 expression was controlled by HIF-1α and contributed to hypoxia-induced increased drug resistance, perhaps explaining why patients with PDK3 overexpression have a greater incidence of treatment failure. Taken together, our findings suggest that PDK3 plays an important role in the metabolic switch and drug resistance of colon cancer and is potentially a novel target for cancer therapy.",
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AU - Lee, Chung-Ta

AU - Lin, Po-Wen

AU - Lee, Jenq-Chang

AU - Tsai, Shaw-Jenq

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