B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway

T. S. Wu, C. T. Tan, C. C. Chang, B. R. Lin, W. T. Lai, S. T. Chen, M. Yen-Ping Kuo, C. L. Rau, F. S. Jaw, H. H. Chang

Research output: Contribution to journalArticle

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Abstract

B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC). However, the regulatory mechanism of BCL10 in OSCC progression is still unknown. Here, we showed that knockdown of endogenous BCL10 could significantly reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we identified S100P as a crucial downstream effector of BCL10-inhibited OSCC progression by high-throughput microarray analysis. S100P messenger RNA and protein expression levels were significantly diminished in silenced-BCL10 clones, and transfected S100P expression plasmids restored migration, invasion, proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore, we provided evidence that BCL10 regulated S100P expression through signal transducers and activators of transcription 1 (STAT1) and activating transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter activity, but showed no effect in truncated STAT1/ATF4 S100P promoter.In addition, we also found that the P50/P65 signaling pathway was involved in BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly reverse P65 activation via outside-in signaling. Taken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC.

Original languageEnglish
Pages (from-to)1207-1219
Number of pages13
JournalOncogene
Volume34
Issue number10
DOIs
Publication statusPublished - Mar 5 2015

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Activating Transcription Factor 4
STAT1 Transcription Factor
B-Cell Leukemia
Mouth Neoplasms
B-Cell Lymphoma
Squamous Cell Carcinoma
Regulatory B-Lymphocytes
Clone Cells
B-Lymphocyte Subsets
Cell Cycle Resting Phase
G1 Phase
Microarray Analysis
Cell Movement
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Wu, T. S., Tan, C. T., Chang, C. C., Lin, B. R., Lai, W. T., Chen, S. T., ... Chang, H. H. (2015). B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway. Oncogene, 34(10), 1207-1219. https://doi.org/10.1038/onc.2014.43

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway. / Wu, T. S.; Tan, C. T.; Chang, C. C.; Lin, B. R.; Lai, W. T.; Chen, S. T.; Yen-Ping Kuo, M.; Rau, C. L.; Jaw, F. S.; Chang, H. H.

In: Oncogene, Vol. 34, No. 10, 05.03.2015, p. 1207-1219.

Research output: Contribution to journalArticle

Wu, TS, Tan, CT, Chang, CC, Lin, BR, Lai, WT, Chen, ST, Yen-Ping Kuo, M, Rau, CL, Jaw, FS & Chang, HH 2015, 'B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway', Oncogene, vol. 34, no. 10, pp. 1207-1219. https://doi.org/10.1038/onc.2014.43
Wu, T. S. ; Tan, C. T. ; Chang, C. C. ; Lin, B. R. ; Lai, W. T. ; Chen, S. T. ; Yen-Ping Kuo, M. ; Rau, C. L. ; Jaw, F. S. ; Chang, H. H. / B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway. In: Oncogene. 2015 ; Vol. 34, No. 10. pp. 1207-1219.
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AU - Lai, W. T.

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