Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma

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...

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Published in:	BMC cancer Vol. 21; no. 1; p. 87
Main Authors:	Kondo, Shunsuke, Hirakawa, Hitoshi, Ikegami, Taro, Uehara, Takayuki, Agena, Shinya, Uezato, Jin, Kinjyo, Hidetoshi, Kise, Noritomo, Yamashita, Yukashi, Tanaka, Katsunori, Hasegawa, Narumi, Kiyuna, Asanori, Maeda, Hiroyuki, Suzuki, Mikio, Gahana, Akira
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 22-01-2021 BioMed Central BMC
Subjects:	Apoptosis Automation Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Carcinoma, Squamous Cell - epidemiology Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - virology Cell Cycle Cell Movement Cell Proliferation Cellular signal transduction Deoxyribonucleic acid Development and progression DNA Female Flow cytometry Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Head & neck cancer Health aspects Human papillomavirus Humans Japan - epidemiology Kinases Male Membrane proteins Metabolism Middle Aged mTOR Oropharyngeal cancer Oropharyngeal Neoplasms - epidemiology Oropharyngeal Neoplasms - metabolism Oropharyngeal Neoplasms - pathology Oropharyngeal Neoplasms - virology Otolaryngology Overall survival Papillomaviridae - isolation & purification Papillomavirus infections Papillomavirus Infections - complications Papillomavirus Infections - virology Penicillin Prognosis Protein kinases Proteins Rapamycin Rapamycin-Insensitive Companion of mTOR Protein - metabolism Raptor Reagents Regulatory-Associated Protein of mTOR - metabolism Rictor Squamous cell carcinoma Survival Rate Targeted cancer therapy Throat cancer Tongue TOR protein Tumor cell lines Tumor Cells, Cultured Japan Human papillomavirus Oropharyngeal cancer Rictor mTOR Rapalog Temsirolimus Overall survival Raptor
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2407 1471-2407
DOI:	10.1186/s12885-021-07794-9