CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation

Hanxiao Shi, Atsuko Niimi, Toshiyuki Takeuchi, Kazuya Shiogama, Yasuyoshi Mizutani, Taisuke Kajino, Kenichi Inada, Tetsunari Hase, Takahiro Hatta, Hirofumi Shibata, Takayuki Fukui, Toyofumi Fengshi Chen-Yoshikawa, Kazuki Nagano, Takashi Murate, Yoshiyuki Kawamoto, Shuta Tomida, Takashi Takahashi, Motoshi Suzuki

Research output: Contribution to journalArticlepeer-review

Abstract

Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y-box as a cis-acting element. As a parallel analysis of database records for 149 non–small-cell lung cancer (NSCLC) cancer patients, we screened for trans-acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer-binding protein γ (CEBPγ) or Y-box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide-dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y-box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.

Original languageEnglish
JournalCancer science
DOIs
Publication statusAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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