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 Rowland Roberts

Research output: Contribution to journalArticle

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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

Fingerprint

transforming growth factors
Epithelial-Mesenchymal Transition
oncogenes
Transforming Growth Factors
hepatoma
Oncogenes
Glioma
Hepatocellular Carcinoma
Transcription Factors
transcription factors
Cells
cells
Phenotype
phenotype
Neoplasms
Up-Regulation
viability
neoplasms
Growth

ASJC Scopus subject areas

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

Cite this

The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism. / Zheng, Xin; Rumie Vittar, Natalia B.; Gai, Xiaohong; Fernandez-Barrena, Maite G.; Moser, Catherine D.; Hu, Chunling; Almada, Luciana L.; McCleary-Wheeler, Angela L.; Elsawa, Sherine F.; Vrabel, Anne M.; Shire, Abdirashid M.; Comba, Andrea; Thorgeirsson, Snorri S.; Kim, Youngsoo; Liu, Qingguang; Fernandez-Zapico, Martin E; Roberts, Lewis Rowland.

In: PLoS One, Vol. 7, No. 11, e49581, 19.11.2012.

Research output: Contribution to journalArticle

Zheng, X, Rumie Vittar, NB, Gai, X, Fernandez-Barrena, MG, Moser, CD, Hu, C, Almada, LL, McCleary-Wheeler, AL, Elsawa, SF, Vrabel, AM, Shire, AM, Comba, A, Thorgeirsson, SS, Kim, Y, Liu, Q, Fernandez-Zapico, ME & Roberts, LR 2012, 'The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism', PLoS One, vol. 7, no. 11, e49581. https://doi.org/10.1371/journal.pone.0049581
Zheng, Xin ; Rumie Vittar, Natalia B. ; Gai, Xiaohong ; Fernandez-Barrena, Maite G. ; Moser, Catherine D. ; Hu, Chunling ; Almada, Luciana L. ; McCleary-Wheeler, Angela L. ; Elsawa, Sherine F. ; Vrabel, Anne M. ; Shire, Abdirashid M. ; Comba, Andrea ; Thorgeirsson, Snorri S. ; Kim, Youngsoo ; Liu, Qingguang ; Fernandez-Zapico, Martin E ; Roberts, Lewis Rowland. / The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism. In: PLoS One. 2012 ; Vol. 7, No. 11.
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