PMID- 33482765 OWN - NLM STAT- MEDLINE DCOM- 20210511 LR - 20210511 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 21 IP - 1 DP - 2021 Jan 22 TI - Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma. PG - 87 LID - 10.1186/s12885-021-07794-9 [doi] LID - 87 AB - BACKGROUND: 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). METHODS: 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. RESULTS: 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 muM 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. CONCLUSIONS: 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. FAU - Kondo, Shunsuke AU - Kondo S AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Hirakawa, Hitoshi AU - Hirakawa H AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Ikegami, Taro AU - Ikegami T AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Uehara, Takayuki AU - Uehara T AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Agena, Shinya AU - Agena S AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Uezato, Jin AU - Uezato J AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Kinjyo, Hidetoshi AU - Kinjyo H AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Kise, Noritomo AU - Kise N AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Yamashita, Yukashi AU - Yamashita Y AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Tanaka, Katsunori AU - Tanaka K AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Hasegawa, Narumi AU - Hasegawa N AD - Ryukyu Society for the Promotion of Oto-Rhino-Laryngology, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Kiyuna, Asanori AU - Kiyuna A AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Maeda, Hiroyuki AU - Maeda H AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. FAU - Suzuki, Mikio AU - Suzuki M AUID- ORCID: 0000-0001-7743-8666 AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. suzuki@med.u-ryukyu.ac.jp. FAU - Gahana, Akira AU - Gahana A AD - Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. AD - Department of Otorhinolaryngology, Head and Neck Surgery, University of Miyazaki, Miyazaki, 889-1692, Japan. LA - eng GR - 168F010007/Japan Society for the Promotion of Science/ GR - 17K11390/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20210122 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Biomarkers, Tumor) RN - 0 (RICTOR protein, human) RN - 0 (RPTOR protein, human) RN - 0 (Rapamycin-Insensitive Companion of mTOR Protein) RN - 0 (Regulatory-Associated Protein of mTOR) SB - IM MH - Apoptosis MH - Biomarkers, Tumor/genetics/*metabolism MH - Carcinoma, Squamous Cell/epidemiology/metabolism/*pathology/virology MH - Cell Cycle MH - Cell Movement MH - Cell Proliferation MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Japan/epidemiology MH - Male MH - Middle Aged MH - Oropharyngeal Neoplasms/epidemiology/metabolism/*pathology/virology MH - Papillomaviridae/*isolation & purification MH - Papillomavirus Infections/*complications/virology MH - Prognosis MH - Rapamycin-Insensitive Companion of mTOR Protein/*metabolism MH - Regulatory-Associated Protein of mTOR/*metabolism MH - Survival Rate MH - Tumor Cells, Cultured PMC - PMC7821513 OTO - NOTNLM OT - Human papillomavirus OT - Oropharyngeal cancer OT - Overall survival OT - Rapalog OT - Raptor OT - Rictor OT - Temsirolimus OT - mTOR COIS- The authors declare that they have no competing interests. EDAT- 2021/01/24 06:00 MHDA- 2021/05/12 06:00 PMCR- 2021/01/22 CRDT- 2021/01/23 05:25 PHST- 2020/03/10 00:00 [received] PHST- 2021/01/05 00:00 [accepted] PHST- 2021/01/23 05:25 [entrez] PHST- 2021/01/24 06:00 [pubmed] PHST- 2021/05/12 06:00 [medline] PHST- 2021/01/22 00:00 [pmc-release] AID - 10.1186/s12885-021-07794-9 [pii] AID - 7794 [pii] AID - 10.1186/s12885-021-07794-9 [doi] PST - epublish SO - BMC Cancer. 2021 Jan 22;21(1):87. doi: 10.1186/s12885-021-07794-9.