@article{8278d6a0be554b459a4ea68f42faa025,
title = "CERS6 required for cell migration and metastasis in lung cancer",
abstract = "Sphingolipids constitute a class of bio-reactive molecules that transmit signals and exhibit a variety of physical properties in various cell types, though their functions in cancer pathogenesis have yet to be elucidated. Analyses of gene expression profiles of clinical specimens and a panel of cell lines revealed that the ceramide synthase gene CERS6 was overexpressed in non–small-cell lung cancer (NSCLC) tissues, while elevated expression was shown to be associated with poor prognosis and lymph node metastasis. NSCLC profile and in vitro luciferase analysis results suggested that CERS6 overexpression is promoted, at least in part, by reduced miR-101 expression. Under a reduced CERS6 expression condition, the ceramide profile became altered, which was determined to be associated with decreased cell migration and invasion activities in vitro. Furthermore, CERS6 knockdown suppressed RAC1-positive lamellipodia/ruffling formation and attenuated lung metastasis efficiency in mice, while forced expression of CERS6 resulted in an opposite phenotype in examined cell lines. Based on these findings, we consider that ceramide synthesis by CERS6 has important roles in lung cancer migration and metastasis.",
keywords = "ceramide, lung cancer, metastasis, micro-RNA",
author = "Motoshi Suzuki and Ke Cao and Seiichi Kato and Naoki Mizutani and Kouji Tanaka and Chinatsu Arima and Tai, {Mei Chee} and Norie Nakatani and Kiyoshi Yanagisawa and Toshiyuki Takeuchi and Hanxiao Shi and Yasuyoshi Mizutani and Atsuko Niimi and Tetsuo Taniguchi and Takayuki Fukui and Kohei Yokoi and Keiko Wakahara and Yoshinori Hasegawa and Yukiko Mizutani and Soichiro Iwaki and Satoshi Fujii and Akira Satou and Keiko Tamiya-Koizumi and Takashi Murate and Mamoru Kyogashima and Shuta Tomida and Takashi Takahashi",
note = "Funding Information: We express our gratefulness to Dr Takahiro Shiraishi (Nagoya University) and Dr Yasuyuki Igarashi (Hokkaido University) for their critical discussion. We also thank Dr Cynthia M. Simbulan-Rosenthal (Georgetown University School of Medicine) for the careful reading of the manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS, 18H02698), a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT, 4701) of Japan, and a Grant-in-Aid for the National Natural Science Foundation of China (81301688). Funding Information: We express our gratefulness to Dr Takahiro Shiraishi (Nagoya University) and Dr Yasuyuki Igarashi (Hokkaido University) for their critical discussion. We also thank Dr Cynthia M. Simbulan‐Rosenthal (Georgetown University School of Medicine) for the careful reading of the manuscript. This work was supported in part by a Grant‐in‐Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS, 18H02698), a Grant‐in‐Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT, 4701) of Japan, and a Grant‐in‐Aid for the National Natural Science Foundation of China (81301688). Publisher Copyright: {\textcopyright} 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd",
year = "2020",
month = oct,
day = "1",
doi = "10.1111/jcmm.15817",
language = "English",
volume = "24",
pages = "11949--11959",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "20",
}
