TY - JOUR
T1 - CERS6 required for cell migration and metastasis in lung cancer
AU - Suzuki, Motoshi
AU - Cao, Ke
AU - Kato, Seiichi
AU - Mizutani, Naoki
AU - Tanaka, Kouji
AU - Arima, Chinatsu
AU - Tai, Mei Chee
AU - Nakatani, Norie
AU - Yanagisawa, Kiyoshi
AU - Takeuchi, Toshiyuki
AU - Shi, Hanxiao
AU - Mizutani, Yasuyoshi
AU - Niimi, Atsuko
AU - Taniguchi, Tetsuo
AU - Fukui, Takayuki
AU - Yokoi, Kohei
AU - Wakahara, Keiko
AU - Hasegawa, Yoshinori
AU - Mizutani, Yukiko
AU - Iwaki, Soichiro
AU - Fujii, Satoshi
AU - Satou, Akira
AU - Tamiya-Koizumi, Keiko
AU - Murate, Takashi
AU - Kyogashima, Mamoru
AU - Tomida, Shuta
AU - Takahashi, Takashi
N1 - Publisher Copyright:
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
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U2 - 10.1111/jcmm.15817
DO - 10.1111/jcmm.15817
M3 - Article
C2 - 32902157
AN - SCOPUS:85090473027
SN - 1582-1838
VL - 24
SP - 11949
EP - 11959
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 20
ER -
