CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation.

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.

• Authors: 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
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 7 Pg. 2770-2780 (Jul 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 33934437 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• CCAAT-Enhancer-Binding Proteins
• CCAAT-enhancer-binding protein-gamma
• Membrane Proteins
• RAC1 protein, human
• RNA, Messenger
• Y-Box-Binding Protein 1
• YBX1 protein, human
• CERS6 protein, human
• Sphingosine N-Acyltransferase
• rac1 GTP-Binding Protein

Topics

• CCAAT-Enhancer-Binding Proteins (metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology, secondary)
• Cell Line, Tumor
• Cell Movement
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Membrane Proteins (genetics, metabolism)
• Neoplasm Invasiveness
• Promoter Regions, Genetic
• Pseudopodia (genetics)
• RNA, Messenger (metabolism)
• Sphingosine N-Acyltransferase (genetics, metabolism)
• Transcriptional Activation
• Up-Regulation
• Y-Box-Binding Protein 1 (genetics, metabolism)
• rac1 GTP-Binding Protein