Association of cancer metabolism-related proteins with oral carcinogenesis - indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?
Association of cancer metabolism-related proteins with oral carcinogenesis - indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?
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DOI：
10.1186/1479-5876-12-208
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发表时间：
2014-07-21
影响因子：
7.4
通讯作者：
Reinert S
中科院分区：
文献类型：
--
作者：
Grimm M;Cetindis M;Lehmann M;Biegner T;Munz A;Teriete P;Kraut W;Reinert S
肿瘤代谢是口腔鳞状细胞癌发生发展的重要因素。IGF-R1、糖酵解相关蛋白的表达（GLUT-1、HK 2、PFK-1、LDHA、TKTL 1）、线粒体酶在正常口腔粘膜（n = 5）、口腔前病变（n = 5）和正常口腔粘膜（n = 5）中分析SDHA、SDHB、ATP合酶。单纯性增生11例;鳞状上皮内瘤变，SIN I-III，n = 35）和OSCC标本（n = 42），通过免疫组织化学和实时聚合酶链反应（qPCR）分析OSCC细胞系。代谢相关蛋白与增殖活性（Ki-67）和凋亡特性（TUNEL法）在口腔鳞癌。通过癌细胞系中的蛋白质印迹证实抗体的特异性。IGF-R1、糖酵解相关蛋白（GLUT-1、HK 2、LDHA、TKTL 1）和线粒体酶（SDHA、SDHB、ATP合成酶）的表达在口腔鳞癌发生发展过程中明显增高。OSCC的代谢活性区域与增殖的癌细胞（Ki-67+）密切相关，但未检测到凋亡（TUNEL法）。本研究首次提供了IGF-R1、糖酵解相关蛋白GLUT-1、HK 2、PFK-1、LDHA和TKTL 1以及线粒体酶SDHA、SDHB和ATP合成酶在OSCC多步骤癌变过程中表达的证据。缺氧相关的糖代谢和线粒体氧化磷酸化特征与口腔鳞癌的发生有关。酸中毒和OXPHOS可能导致代谢向磷酸戊糖途径（PPP）转变。因此，天然化合物或合成维生素衍生物对PPP、糖酵解和靶向抗线粒体治疗（ROS生成）的抑制可能作为OSCC辅助治疗介导的癌细胞凋亡的敏化剂。
Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC.
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影响因子：
3.4
作者：
Beck, Raphael;Pedrosa, Rozangela Curi;Verrax, Julien
通讯作者：
Verrax, Julien
影响因子：
2
作者：
Bhattarai, Govinda;Lee, Young-Hee;Yi, Ho-Keun
通讯作者：
Yi, Ho-Keun
影响因子：
2.8
作者：
Bruening, Ansgar
通讯作者：
Bruening, Ansgar
DOI：
10.1007/s10856-007-3351-8
发表时间：
2008-03-01
影响因子：
3.7
作者：
Alexander, Dorothea;Hoffmann, Juergen;Reinert, Siegmar
通讯作者：
Reinert, Siegmar
影响因子：
7.3
作者：
ANSARI, B;COATES, PJ;HALL, PA
通讯作者：
HALL, PA