論文 - 詳細
| RRC ID | 36952 |
|---|---|
| 著者 | Fukuda S, Miyata H, Miyazaki Y, Makino T, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Takiguchi S, Mori M, Doki Y. |
| タイトル | Pyruvate Kinase M2 Modulates Esophageal Squamous Cell Carcinoma Chemotherapy Response by Regulating the Pentose Phosphate Pathway. |
| ジャーナル | Ann Surg Oncol |
| Abstract |
BACKGROUND:Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme that regulates the Warburg effect and is necessary for tumor growth. However, its role in chemoresistance has not been fully elucidated. METHODS:PKM2 expression was examined by immunohistochemistry in 205 tissue samples from thoracic esophageal squamous cell carcinoma patients who had undergone curative surgery (100 patients with surgery alone and 105 patients with preoperative chemotherapy). The relationship between PKM2 expression and clinicopathological factors, including chemotherapy response was examined. In vitro assays were performed to determine the mechanism of PKM2-related chemoresistance, using esophageal squamous cell carcinoma cell lines. RESULTS:PKM2 expression significantly correlated with tumor cell differentiation, tumor depth, and tumor stage. Strong PKM2 expression significantly correlated with decreased survival rates and poor response to chemotherapy. In vitro assays showed that PKM2 inhibition significantly decreased cisplatin resistance and increased apoptosis. In siPKM2-transfected cells, pyruvate kinase activity paradoxically increased, followed by increased intracellular reactive oxygen species levels. The ratio of NADPH/NADP, which is an indicator of glucose influx into pentose phosphate pathway (PPP), significantly decreased in siPKM2-transfected cells upon cisplatin treatment compared with control cells. CONCLUSIONS:PKM2 expression is associated with esophageal squamous cell carcinoma chemoresistance. PKM2 inhibition can restore cisplatin sensitivity by inactivating PPP. |
| 巻・号 | 22 Suppl 3 |
| ページ | S1461-8 |
| 公開日 | 2015-12-1 |
| DOI | 10.1245/s10434-015-4522-3 |
| PII | 10.1245/s10434-015-4522-3 |
| PMID | 25808097 |
| MeSH | Antineoplastic Agents / pharmacology Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Blotting, Western Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Proliferation / drug effects Cisplatin / pharmacology Drug Resistance, Neoplasm Esophageal Neoplasms / drug therapy Esophageal Neoplasms / metabolism Esophageal Neoplasms / pathology* Gene Expression Regulation, Neoplastic / drug effects Glycolysis / drug effects Humans Immunoenzyme Techniques Membrane Proteins / genetics Membrane Proteins / metabolism* Neoplasm Invasiveness Neoplasm Staging Pentose Phosphate Pathway / drug effects* Phosphorylation / drug effects Prognosis RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Survival Rate Thyroid Hormones / genetics Thyroid Hormones / metabolism* Tumor Cells, Cultured |
| IF | 4.061 |
| 引用数 | 22 |
| WOS 分野 | SURGERY ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | TE-5(RCB1949) TE-6(RCB1950) TE-8(RCB2098) TE-9(RCB1988) TE-15(RCB1951) |