Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma. Issue 6 (1st May 2018)

• Record Type: Journal Article
• Authors: Nakashima, Chie; Yamamoto, Kazuhiko; Fujiwara‐Tani, Rina; Luo, Yi; Matsushima, Sayako; Fujii, Kiyomu; Ohmori, Hitoshi; Sasahira, Tomonori; Sasaki, Takamitsu; Kitadai, Yasuhiko; Kirita, Tadaaki; Kuniyasu, Hiroki
• Is Part Of: Cancer science. Volume 109:Issue 6(2018)
• Page Start: 2036
• Page End: 2045
• Publication Date: 2018-05-01
• Subjects: cancer invasion -- glutamine -- malic enzyme -- prognosis -- stemness; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13594
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Malic enzyme 1 (ME1) is a multifunctional protein involved in glycolysis, the citric acid cycle, NADPH production, glutamine metabolism, and lipogenesis. It is overexpressed in various cancers. We examined the expression of ME1 in 119 oral squamous cell carcinomas (OSCCs) using immunohistochemistry. Malic enzyme 1 expression was moderate to strong in 57 (48%) OSCCs and correlated with pT, pN, clinical stage, and histological grade. In 37 cases with prognostic evaluation, moderate to strong ME1 expression indicated a worse prognosis than did weak ME1 expression. Malic enzyme 1 knockdown or inactivation by lanthanide inhibited cell proliferation and motility and suppressed the epithelial‐mesenchymal transition in HSC3 human OSCC cells. Knockdown of ME1 also shifted energy metabolism from aerobic glycolysis and lactate fermentation to mitochondrial oxidative phosphorylation, and the redox status from reductive to oxidative. In a mouse tumor model, lanthanide suppressed tumor growth and increased survival time. These findings reveal that ME1 is a valid target for molecular therapy in OSCC. Abstract : Malic enzyme 1 (ME1) expression is associated with disease progression in oral squamous cell carcinomas (OSCC). ME1 participates to maintain aerobic glycolysis and reductive redox status, and enhances epithelial‐mesenchymal transition and stemness in OSCC cells. Inhibition of ME1 suppressed tumor growth and increased survival time.