The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism

Xin Zheng, Natalia B. Rumie Vittar, Xiaohong Gai, Maite G. Fernandez-Barrena, Catherine D. Moser, Chunling Hu, Luciana L. Almada, Angela L. McCleary-Wheeler, Sherine F. Elsawa, Anne M. Vrabel, Abdirashid M. Shire, Andrea Comba, Snorri S. Thorgeirsson, Youngsoo Kim, Qingguang Liu, Martin E. Fernandez-Zapico, Lewis R. Roberts

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however the regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation of SNAI1 and serves as a downstream effector of the transforming growth factor-β1 (TGFβ1) pathway, a well-known regulator of EMT in cancer cells. Overexpression of GLI1 increased proliferation, viability, migration, invasion, and colony formation by HCC cells. Conversely, GLI1 knockdown led to a decrease in all the above-mentioned cancer-associated phenotypes in HCC cells. Further analysis of GLI1 regulated cellular functions showed that this transcription factor is able to induce EMT and identified SNAI1 as a transcriptional target of GLI1 mediating this cellular effect in HCC cells. Moreover, we demonstrated that an intact GLI1-SNAI1 axis is required by TGFβ1 to induce EMT in these cells. Together, these findings define a novel cellular mechanism regulated by GLI1, which controls the growth and EMT phenotype in HCC.

Original languageEnglish (US)
Article numbere49581
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 19 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism'. Together they form a unique fingerprint.

  • Cite this

    Zheng, X., Rumie Vittar, N. B., Gai, X., Fernandez-Barrena, M. G., Moser, C. D., Hu, C., Almada, L. L., McCleary-Wheeler, A. L., Elsawa, S. F., Vrabel, A. M., Shire, A. M., Comba, A., Thorgeirsson, S. S., Kim, Y., Liu, Q., Fernandez-Zapico, M. E., & Roberts, L. R. (2012). The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism. PloS one, 7(11), [e49581]. https://doi.org/10.1371/journal.pone.0049581