Abstract |
Colon cancer is one of the deadliest cancers worldwide because of its metastasis to other essential organs. Metastasis of colon cancer involves a complex set of events, including epithelial-to-mesenchymal transition (EMT) that increases invasiveness of the tumor cells. Here, we show that the xeroderma pigmentosum group E ( XPE) gene product, damaged DNA-binding protein (DDB)-2, is downregulated in high-grade colon cancers, and it plays a dominant role in the suppression of EMT of the colon cancer cells. Depletion of DDB2 promotes mesenchymal phenotype, whereas expression of DDB2 promotes epithelial phenotype. DDB2 constitutively represses genes that are the key activators of EMT, indicating that DDB2 is a master regulator of EMT of the colon cancer cells. Moreover, we observed evidence that DDB2 functions as a barrier for EMT induced by hypoxia and TGF-β. Also, we provide evidence that DDB2 inhibits metastasis of colon cancer. The results presented here identify a transcriptional regulatory pathway of DDB2 that is directly linked to the mechanisms that suppress metastasis of colon cancer.
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Authors | Nilotpal Roy, Prashant V Bommi, Uppoor G Bhat, Shaumick Bhattacharjee, Indira Elangovan, Jing Li, Krushna C Patra, Dragana Kopanja, Adam Blunier, Richard Benya, Srilata Bagchi, Pradip Raychaudhuri |
Journal | Cancer research
(Cancer Res)
Vol. 73
Issue 12
Pg. 3771-82
(Jun 15 2013)
ISSN: 1538-7445 [Electronic] United States |
PMID | 23610444
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | ©2013 AACR. |
Chemical References |
- Cadherins
- DDB2 protein, human
- DNA-Binding Proteins
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Topics |
- Animals
- Blotting, Western
- Cadherins
(metabolism)
- Cell Hypoxia
- Cell Line, Tumor
- Colonic Neoplasms
(genetics, metabolism, pathology)
- DNA-Binding Proteins
(genetics, metabolism)
- Epithelial-Mesenchymal Transition
(genetics)
- Gene Expression Regulation, Neoplastic
- HCT116 Cells
- Humans
- Immunohistochemistry
- Lung Neoplasms
(genetics, metabolism, secondary)
- Male
- Mammary Neoplasms, Experimental
(genetics, metabolism, pathology)
- Mice
- Mice, Nude
- Mice, SCID
- Neoplasm Invasiveness
- RNA Interference
- Reverse Transcriptase Polymerase Chain Reaction
- Transplantation, Heterologous
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