Analysis of proliferation and progression mechanisms in oral cancer which targeted fatty acid synthesis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09822
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Meikai University
• Principal Investigator: Fukuda Masakatsu 明海大学, 歯学部, 講師 (10311614)
• Co-Investigator(Kenkyū-buntansha): 坂下 英明 明海大学, 歯学部, 教授 (10178551) ; 大森 喜弘 明海大学, 歯学部, 教授 (50194311)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 口腔癌 / 脂肪酸合成酵素（FAS） / p53 / SREBP / 細胞死 / Resveratrol / E-FABP

Outline of Final Research Achievements

This study examined molecularbiologically the mechanisms of proliferation and progression in squamous cell carcinoma of the oral cavity. The strong expression of Fatty Acid Synthase (FAS) and SREBP1 were observed in Ca9-22 cell line. When SREBP1 expression were knockdowned, the expression of FAS and E-FABP were downregulated, consequently the proliferative activity of Ca9-22 cells was inhibited.
Furthermore, the positive immunoreactivities of FAS and SREBP1 were observed in human oral squamous cell carcinoma (HOSCC) tissues, and they were almost consistent with p53 positive (mutated) cases. In conclusion, it can therefore be hypothesized, based on both the present in vitro and in vivo observations, that a loss of p53 function results in SREBP1 activation, thereby upregulating FAS, and consequently, may promote HOSCC tumorigenesis.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

多くの癌細胞がグルコース代謝を亢進させて主なエネルギー供給源として増殖していることは，ワールブルグ効果としてよく知られている．ところが本研究において，脂肪酸合成も口腔癌のエネルギー源として重要な役割を担っていることが確認された．そこで，赤ブドウの抽出液中に多く含まれるポリフェノールで，脂質代謝の改善作用を示すResveratrolを口腔癌細胞に作用させた際，腫瘍細胞に対して強い毒性を認めたものの，正常細胞にはほとんど無害であった．この事実は，より広い学術，あるいは癌患者のQOLの向上といった医療を通じた大きな社会的意義を持つと考える．