Transcription factor SPZ1 promotes TWIST-mediated epithelial-mesenchymal transition and oncogenesis in human liver cancer

L. T. Wang, S. S. Chiou, C. Y. Chai, E. Hsi, C. M. Chiang, S. K. Huang, S. N. Wang, K. K. Yokoyama, S. H. Hsu

Research output: Contribution to journalArticle

Abstract

The epithelial-mesenchymal transition (EMT) is an important process in the progression of cancer. However, its occurrence and mechanism of regulation are not fully understood. We propose a regulatory pathway in which spermatogenic leucine zipper 1 (SPZ1) promotes EMT through its transactivating ability in increasing TWIST1 expression. We compared the expression of SPZ1 and TWIST1 in specimens of hepatocarcinoma cells (HCCs) and non-HCCs. Expression of SPZ1 exhibited a tumor-specific expression pattern and a high correlation with patients' survival time, tumor size, tumor number and progression stage. Moreover, forced expression and knockdown of SPZ1 in hepatoma cells showed that SPZ1 was able to regulate the cellular proliferation, invasion, and tumorigenic activity in a TWIST1-dependent manner in vitro and in vivo. These data demonstrate that SPZ1, a newly dscribed molecule, transactivates TWIST1 promoters, and that this SPZ1-TWIST axis mediates EMT signaling and exerts significant regulatory effects on tumor oncogenesis.

Original languageEnglish (US)
Pages (from-to)4405-4414
Number of pages10
JournalOncogene
Volume36
Issue number31
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Wang, L. T., Chiou, S. S., Chai, C. Y., Hsi, E., Chiang, C. M., Huang, S. K., Wang, S. N., Yokoyama, K. K., & Hsu, S. H. (2017). Transcription factor SPZ1 promotes TWIST-mediated epithelial-mesenchymal transition and oncogenesis in human liver cancer. Oncogene, 36(31), 4405-4414. https://doi.org/10.1038/onc.2017.69