title: DDB2 suppresses epithelial-to-mesenchymal transition in colon cancer.
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.
authors.affiliation: Department of Biochemistry and Molecular Genetics; Center of Molecular Biology of Oral Diseases College of Dentistry, Cancer Center; and Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Nilotpal
authors.initials: N
authors.lastname: Roy
authors.forename: Prashant V
authors.initials: PV
authors.lastname: Bommi
authors.forename: Uppoor G
authors.initials: UG
authors.lastname: Bhat
authors.forename: Shaumick
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Indira
authors.initials: I
authors.lastname: Elangovan
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Krushna C
authors.initials: KC
authors.lastname: Patra
authors.forename: Dragana
authors.initials: D
authors.lastname: Kopanja
authors.forename: Adam
authors.initials: A
authors.lastname: Blunier
authors.forename: Richard
authors.initials: R
authors.lastname: Benya
authors.forename: Srilata
authors.initials: S
authors.lastname: Bagchi
authors.forename: Pradip
authors.initials: P
authors.lastname: Raychaudhuri
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D015820:Cadherins; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins