title: Therapeutic implication of mTORC2 in oral squamous cell carcinoma.
abstract: The aim of the present study was to clarify the association of mTORC2 expression with the cancer progression and the anti-tumor effects of Torin-1 alone and combined treatment with Cetuximab in OSCC cells. The expressions of Rictor and SGK1 were immunohistochemically evaluated and the relationships between the expressions of molecular markers and clinicopathological factors were determined. Moreover, OSCC cells were treated with Torin-1, Cetuximab or combined agents, and anti-tumor effects of OSCC cells were examined in vitro and in vivo. Rictor and SGK1 expressions were significantly associated with tumor stage and pattern of invasion in OSCC sections (P<0.05 and P<0.01, respectively). Treatment of OSCC cell lines with Torin-1 resulted in dose and time-dependent inhibition of proliferation with decrease of phosphorylation on downstream molecules. Combined treatment with Torin-1 and Cetuximab resulted in enhanced anti-tumor effects in vitro compared with either agent alone. Furthermore, treatment of mice bearing OSCC xenografts with Torin-1 and Cetuximab also demonstrated a remarked growth inhibition of tumor volumes. The results suggested that new regimens of systemic therapy combined with Cetuximab and Torin-1 may be useful for very advanced OSCC patients.
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. Electronic address: naruse12@nagasaki-u.ac.jp.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Okuyama
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Omori
authors.affiliation: Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakao
authors.affiliation: Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Yamada
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
mesh_terms: D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000076225:Mechanistic Target of Rapamycin Complex 2
keywords: Cetuximab; Rictor; SGK1; Torin-1; mTORC2