1. CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation
- Author
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Takashi Murate, Atsuko Niimi, Toshiyuki Takeuchi, Takayuki Fukui, Yasuyoshi Mizutani, Tetsunari Hase, Ken Ichi Inada, Hanxiao Shi, Kazuya Shiogama, Shuta Tomida, Taisuke Kajino, Motoshi Suzuki, Toyofumi F. Chen-Yoshikawa, Takashi Takahashi, Yoshiyuki Kawamoto, Hirofumi Shibata, Takahiro Hatta, and Kazuki Nagano
- Subjects
0301 basic medicine ,Transcriptional Activation ,rac1 GTP-Binding Protein ,Cancer Research ,Lung Neoplasms ,Biology ,Metastasis ,YBX1 ,03 medical and health sciences ,0302 clinical medicine ,Cell, Molecular, and Stem Cell Biology ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Sphingosine N-Acyltransferase ,medicine ,Gene silencing ,metastasis ,Humans ,Neoplasm Invasiveness ,Pseudopodia ,RNA, Messenger ,Lung cancer ,Promoter Regions, Genetic ,Transcription factor ,Gene knockdown ,CEBPγ ,Cancer ,Membrane Proteins ,Promoter ,General Medicine ,Original Articles ,medicine.disease ,Up-Regulation ,lung cancer ,030104 developmental biology ,Oncology ,CERS6 ,030220 oncology & carcinogenesis ,Cancer research ,CCAAT-Enhancer-Binding Proteins ,Adenocarcinoma ,Original Article ,Y-Box-Binding Protein 1 - 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., Schematic illustration showing CEBPγ functions for cancer cell migration.
- Published
- 2021