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Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers.
Zhong, Yali; Li, Xiaoli; Ji, Yasai; Li, Xiaoran; Li, Yaqing; Yu, Dandan; Yuan, Yuan; Liu, Jian; Li, Huixiang; Zhang, Mingzhi; Ji, Zhenyu; Fan, Dandan; Wen, Jianguo; Goscinski, Mariusz Adam; Yuan, Long; Hao, Bin; Nesland, Jahn M; Suo, Zhenhe.
Afiliación
  • Zhong Y; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Li X; Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Ji Y; Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway.
  • Li X; Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Li Y; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Yu D; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Yuan Y; Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway.
  • Liu J; Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Li H; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Zhang M; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Ji Z; Department of Pathology, Capital Medical University, Beijing, China.
  • Fan D; Institute of Health Quarantine, Chinese Academy of Inspection and Quarantine, Beijing, China.
  • Wen J; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Goscinski MA; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • Yuan L; Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou.
  • Hao B; Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou.
  • Nesland JM; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China.
  • Suo Z; Department of Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Oncotarget ; 8(8): 13344-13356, 2017 Feb 21.
Article en En | MEDLINE | ID: mdl-28076853
Cells generate adenosine-5'-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the "Warburg Effect", in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1). To further analyze the function of PDHA1 in cancer cells, it was knock out (KO) in the human prostate cancer cell line LnCap and a stable KO cell line was established. We demonstrated that PDHA1 gene KO significantly decreased mitochondrial OXPHOS and promoted anaerobic glycolysis, accompanied with higher stemness phenotype including resistance to chemotherapy, enhanced migration ability and increased expression of cancer stem cell markers. We also examined PDHA1 protein expression in prostate cancer tissues by immunohistochemistry and observed that reduced PDHA1 protein expression in clinical prostate carcinomas was significantly correlated with poor prognosis. Collectively, our results show that negative PDHA1 gene expressionis associated with significantly higher cell stemness in prostate cancer cells and reduced protein expression of this gene is associated with shorter clinical outcome in prostate cancers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Células Madre Neoplásicas / Piruvato Deshidrogenasa (Lipoamida) Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Células Madre Neoplásicas / Piruvato Deshidrogenasa (Lipoamida) Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos