Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.
Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.
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DOI：
10.1186/s12885-021-07794-9
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发表时间：
2021-01-22
期刊：
影响因子：
3.8
通讯作者：
Gahana A
中科院分区：
文献类型：
--
作者：
Kondo S;Hirakawa H;Ikegami T;Uehara T;Agena S;Uezato J;Kinjyo H;Kise N;Yamashita Y;Tanaka K;Hasegawa N;Kiyuna A;Maeda H;Suzuki M;Gahana A
尽管有报道称人乳头瘤病毒（HPV）感染与雷帕霉素（mTOR）信号转导激活的机制靶点之间存在联系，但mTOR通路，特别是raptor和rictor在HPV相关头颈癌中的作用仍不清楚。本研究的目的是阐明mTOR通路在HPV相关口咽鳞状细胞癌（OPSCC）中的作用。本研究涉及两种策略。第一个是研究mTOR和mTOR相关复合物在高危HPV阳性（UM-SCC 47和CaSki）和HPV阴性（SCC-4和SAS）癌细胞系中的活性。第二是阐明mTOR复合物在80例口咽癌组织中的表达，并研究mTOR复合物表达与OPSCC患者生存率之间的关系。UM-SCC 47和CaSki细胞系显示raptor基因和蛋白的高表达。在与6 μM坦西罗莫司（雷帕霉素类似物）孵育24 h后，它们也表现出G1/S和G2/M期细胞周期阻滞，坦西罗莫司给药抑制了它们的生长。与HPV无关的OPSCC相比，HPV相关的OPSCC样本显示raptor和rictor的基因和蛋白表达较高。此外，raptor和rictor高表达的HPV相关OPSCC患者的预后往往比低或中等表达的患者更差。这些结果表明raptor和rictor在HPV相关OPSCC中具有重要作用，并且替西罗莫司是HPV相关OPSCC患者的潜在治疗剂。这是第一个报告揭示raptor和rictor在HPV相关的OPSCC中的过度表达。在线版本包含补充材料，可通过10.1186/s12885-021-07794-9获得。
Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC). The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC. The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression. These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC. The online version contains supplementary material available at 10.1186/s12885-021-07794-9.
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影响因子：
3.5
作者：
Ang, Kie Kian;Sturgis, Erich M.
通讯作者：
Sturgis, Erich M.
影响因子：
3.1
作者：
Kaibori, Masaki;Shikata, Nobuaki;Kon, Masanori
通讯作者：
Kon, Masanori
DOI：
10.1056/nejmoa0912217
发表时间：
2010-07-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ang KK;Harris J;Wheeler R;Weber R;Rosenthal DI;Nguyen-Tân PF;Westra WH;Chung CH;Jordan RC;Lu C;Kim H;Axelrod R;Silverman CC;Redmond KP;Gillison ML
通讯作者：
Gillison ML
影响因子：
8.1
作者：
Elghazi L;Blandino-Rosano M;Alejandro E;Cras-Méneur C;Bernal-Mizrachi E
通讯作者：
Bernal-Mizrachi E
影响因子：
45.3
作者：
Chaturvedi, Anil K.;Engels, Eric A.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.