| Title |
The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism
|
|---|---|
| Published in |
PLOS ONE, November 2012
|
| DOI | 10.1371/journal.pone.0049581 |
| Pubmed ID | |
| Authors |
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 |
| 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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 53 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 23% |
| Researcher | 9 | 17% |
| Student > Bachelor | 8 | 15% |
| Student > Master | 6 | 11% |
| Student > Doctoral Student | 4 | 8% |
| Other | 5 | 9% |
| Unknown | 9 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 14 | 26% |
| Biochemistry, Genetics and Molecular Biology | 9 | 17% |
| Medicine and Dentistry | 9 | 17% |
| Neuroscience | 2 | 4% |
| Engineering | 2 | 4% |
| Other | 4 | 8% |
| Unknown | 13 | 25% |