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Retraction Free access | 10.1172/JCI133806

Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells

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, and Takashi Takahashi

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Published November 1, 2019 - More info

Published in Volume 129, Issue 11 on November 1, 2019
J Clin Invest. 2019;129(11):5050–5050. https://doi.org/10.1172/JCI133806.
© 2019 American Society for Clinical Investigation
Published November 1, 2019 - Version history
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Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells
Motoshi Suzuki, … , Mamoru Kyogashima, Takashi Takahashi
Motoshi Suzuki, … , Mamoru Kyogashima, Takashi Takahashi
Research Article Oncology

Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells

Abstract

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 l-α-dimyristoylphosphatidylcholine liposome and the glucosylceramide synthase inhibitor D-PDMP induced cell death in association with ceramide accumulation and promoted cancer cell apoptosis and tumor regression in murine models. Together, these results indicate that CERS6-dependent ceramide synthesis and maintenance of ceramide in the cellular membrane are essential for lamellipodia formation and metastasis. Moreover, these results suggest that targeting this homeostasis has potential as a therapeutic strategy for CERS6-overexpressing NSCLC.

Authors

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 retraction: J Clin Invest. 2019;129(11):5050. https://doi.org/10.1172/JCI133806

At the request of the corresponding author, the JCI is retracting this article. Following an institutional investigative review of errors in the article, it was determined that the data reported in Figure 1B were an analysis of E2F1 expression rather than CERS6 expression, as originally reported. The correct data do not show a difference in CERS6 expression with invasion status in human lung adenocarcinomas. In addition, errors were noted in Supplemental Figure 2, Supplemental Figure 3B, and Supplemental Table 1. The institutional review found no evidence of intention to falsify results.

The authors apologize for these errors.

Footnotes

See the related article at Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells.

Version history
  • Version 1 (November 1, 2019): Print issue publication
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