Regulatory Role of Pyruvate Dehydrogenase During Head and Neck Carcinogenesis
| Autor: | Jian-Min Huang, '黃建旻 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 While normal cells utilize mitochondrial energy, cancer cells exhibited less mitochondrial activity and preferentially obtain cellular fuel from glycolysis. Owing to this physiological variance, recent studies suggested that glycolytic enzymes could be potential anti-cancer targets; however, whether manipulation of mitochondrial proteins could modulate cancer cell malignancy is still unknown. Pyruvate dehydrogenase E1 component α subunit (PDHA1) is a catalytic subunit of mitochondrial pyruvate dehydrogenase complex that converts pyruvate into acetyl-CoA to enter into Tri Carboxylic Acid (TCA) cycle. Current study aimed to define the regulation of PDHA1 for head and neck (H&;N) carcinogenesis. PDHA1 is inactive in 4-Nitroquinoline 1-oxide induced hyperplastic tongue epithelium, human oral sqamous cell carcinoma as well as inhuman hepatocellular carcinoma suggesting the decreased expression of PDHA1 could be essential during carcinogenesis. Multifaceted cellular cues were analyzed in PDHA1 deficient and PDHA1 over-activated H&;N cancer cells. The results showed that loss of PDHA1 led to (1) increased cell growth; (2) upregulated cell motility;(3) lower expression of differentiation marker involucrin and (4)up-regulated resistance for the chemotherapeutic drug cisplatin and 5-FU implying that PDHA1 could potentially inhibit cell malignancy in H&;N cancer cells. In vivo analysis showed that PDHA1 deficient xenografic tumor cancer cells exhibited larger tumor size and greater tumor weight. Taken together. PDHA1 deficiency promoted H&;N cancer cell malignancy and the outcomes could pave a way in developing mitochondria-mediated anti-cancer treatment for H&;N cancer. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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