First published July 2, 2019 - More info
Sphingolipids make up a family of molecules associated with an array of biological functions, including cell death and migration. Sphingolipids are often altered in cancer, though how these alterations lead to tumor formation and progression is largely unknown. Here, we analyzed non–small-cell lung cancer (NSCLC) specimens and cell lines and determined that ceramide synthase 6 (CERS6) is markedly overexpressed compared with controls. Elevated CERS6 expression was due in part to reduction of microRNA-101 (miR-101) and was associated with increased invasion and poor prognosis. CERS6 knockdown in NSCLC cells altered the ceramide profile, resulting in decreased cell migration and invasion in vitro, and decreased the frequency of RAC1-positive lamellipodia formation while CERS6 overexpression promoted it. In murine models, CERS6 knockdown in transplanted NSCLC cells attenuated lung metastasis. Furthermore, combined treatment with
Motoshi Suzuki, Ke Cao, Seiichi Kato, Yuji Komizu, Naoki Mizutani, Kouji Tanaka, Chinatsu Arima, Mei Chee Tai, Kiyoshi Yanagisawa, Norie Togawa, Takahiro Shiraishi, Noriyasu Usami, Tetsuo Taniguchi, Takayuki Fukui, Kohei Yokoi, Keiko Wakahara, Yoshinori Hasegawa, Yukiko Mizutani, Yasuyuki Igarashi, Jin-ichi Inokuchi, Soichiro Iwaki, Satoshi Fujii, Akira Satou, Yoko Matsumoto, Ryuichi Ueoka, Keiko Tamiya-Koizumi, Takashi Murate, Mitsuhiro Nakamura, Mamoru Kyogashima, Takashi Takahashi
Original citation: J Clin Invest. 2016;126(1):254–265. https://doi.org/10.1172/JCI79775
Citation for this expression of concern: J Clin Invest. 2019;129(8):3464 https://doi.org/10.1172/JCI131245
The corresponding author recently notified the JCI that the patient data presented in Figure 1B were not correct. Analysis of the correct patient data set does not show a significant difference in CERS6 expression in human lung adenocarcinomas with positive invasive growth (definite) compared with those with negligible invasive growth or without invasive growth (focal/none). The Editors have requested an institutional investigation into this matter, and we will inform our readers of the outcome when the investigation is complete.
See the related article at Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells.