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 |
| 卷 | 179 |
| 發行號 | 3 |
| DOIs | |
| 出版狀態 | Published - 2011 九月 1 |
指紋
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
引用此文
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Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. / Lu, Chun Wun; Lin, Shao-Chieh; Chien, Chun Wei; Lin, Shih-Chieh; Lee, Chung-Ta; Lin, Po-Wen; Lee, Jenq-Chang; Tsai, Shaw-Jenq.
於: American Journal of Pathology, 卷 179, 編號 3, 01.09.2011, p. 1405-1414.研究成果: Article
TY - JOUR
T1 - Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer
AU - Lu, Chun Wun
AU - Lin, Shao-Chieh
AU - Chien, Chun Wei
AU - Lin, Shih-Chieh
AU - Lee, Chung-Ta
AU - Lin, Po-Wen
AU - Lee, Jenq-Chang
AU - Tsai, Shaw-Jenq
PY - 2011/9/1
Y1 - 2011/9/1
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=80052845698&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2011.05.050
DO - 10.1016/j.ajpath.2011.05.050
M3 - Article
C2 - 21763680
AN - SCOPUS:80052845698
VL - 179
SP - 1405
EP - 1414
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -