PMID- 30410671
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 78
DP  - 2018 Oct 5
TI  - DDB2 regulates Epithelial-to-Mesenchymal Transition (EMT) in Oral/Head and Neck 
      Squamous Cell Carcinoma.
PG  - 34708-34718
LID - 10.18632/oncotarget.26168 [doi]
AB  - DDB2 is a sensor of DNA damage and it plays an important role in Global Genomic 
      Repair (GG-NER). Our previous studies show that DDB2 is involved in the 
      regulation of metastasis in colon adenocarcinoma. Squamous Cell Carcinomas in the 
      Oral/Head & Neck region (HNSCC) are particularly aggressive due to high incidence 
      of recurrence and distant metastasis. In this study, we show that DDB2 expression 
      is downregulated in advanced HNSCCs and loss of DDB2 expression coincides with 
      reduced survival. Recent meta-analysis of gene expression data characterized the 
      mesenchymal-type (EMT-type) as one most aggressive cancer cluster in HNSCC. Here, 
      we report that DDB2 constitutively represses mRNA expression of the EMT- 
      regulatory transcription factors SNAIL, ZEB1, and angiogenic factor VEGF in HNSCC 
      cells. As a result, re-expression of DDB2 in metastatic cells reversed EMT with 
      transcriptional upregulation of epithelial marker E-cadherin, and downregulation 
      of mesenchymal markers N-cadherin, Vimentin, and Fibronectin. Interestingly, in a 
      reverse assay, depletion of DDB2 in non-metastatic cells induced expression of 
      the same EMT-regulatory transcription factors. TGFbetas are major regulators of 
      Snail and Zeb1, and we observed that DDB2 transcriptionally regulates expression 
      of TGFB2 in HNSCC cells. Re-expression of DDB2 in mouse embryonic fibroblasts 
      (MEFs) isolated from Ddb2 (-/-) knockout-mice resulted in repression of 
      EMT-regulatory factors Zeb1, Snail and Tgfb2. Taken together, these results 
      support the active role of DDB2 as a candidate suppressor of the EMT-process in 
      HNSCC. Early detection leads to significantly higher survival in HNSCC and DDB2 
      expression in tumors can be a predictor of EMT progression.
FAU - Bommi, Prashant V
AU  - Bommi PV
AD  - Department of Oral Biology, College of Dentistry, University of Illinois at 
      Chicago, Chicago, Illinois, USA.
AD  - Current Address: Department of Clinical Cancer Prevention, Biological Sciences 
      Research Building (BSRB), University of Texas MD Anderson Cancer Center, Houston, 
      Texas.
FAU - Ravindran, Sriram
AU  - Ravindran S
AD  - Department of Oral Biology, College of Dentistry, University of Illinois at 
      Chicago, Chicago, Illinois, USA.
FAU - Raychaudhuri, Pradip
AU  - Raychaudhuri P
AD  - Department of Biochemistry and Molecular Genetics, College of Medicine, 
      University of Illinois at Chicago, Chicago, Illinois, USA.
FAU - Bagchi, Srilata
AU  - Bagchi S
AD  - Department of Oral Biology, College of Dentistry, University of Illinois at 
      Chicago, Chicago, Illinois, USA.
LA  - eng
GR  - R01 CA156164/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20181005
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC6205178
OTO - NOTNLM
OT  - damaged DNA binding protein 2 (DDB2)
OT  - epithelial-to-mesenchymal transition (EMT)
OT  - oral/head and neck squamous cell carcinoma (HNSCC)
OT  - transforming growth factor beta (TGFbeta)
OT  - tumor suppressor
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2018/11/10 06:00
MHDA- 2018/11/10 06:01
PMCR- 2018/10/05
CRDT- 2018/11/10 06:00
PHST- 2018/06/09 00:00 [received]
PHST- 2018/09/08 00:00 [accepted]
PHST- 2018/11/10 06:00 [entrez]
PHST- 2018/11/10 06:00 [pubmed]
PHST- 2018/11/10 06:01 [medline]
PHST- 2018/10/05 00:00 [pmc-release]
AID - 26168 [pii]
AID - 10.18632/oncotarget.26168 [doi]
PST - epublish
SO  - Oncotarget. 2018 Oct 5;9(78):34708-34718. doi: 10.18632/oncotarget.26168. 
      eCollection 2018 Oct 5.