PMID- 29339729
OWN - NLM
STAT- MEDLINE
DCOM- 20190617
LR  - 20240313
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 2
DP  - 2018 Jan 16
TI  - Ecotropic viral integration site 1 promotes metastasis independent of epithelial 
      mesenchymal transition in colon cancer cells.
PG  - 18
LID - 10.1038/s41419-017-0036-1 [doi]
LID - 18
AB  - The most indecipherable component of solid cancer is the development of 
      metastasis which accounts for more than 90% of cancer-related mortalities. A 
      developmental program termed epithelial-mesenchymal transition (EMT) has also 
      been shown to play a critical role in promoting metastasis in epithelium-derived 
      solid tumors. By analyzing publicly available microarray datasets, we observed 
      that ecotropic viral integration site 1 (EVI1) correlates negatively with SLUG, a 
      master regulator of EMT. This correlation was found to be relevant as we 
      demonstrated that EVI1 binds to SLUG promoter element directly through the distal 
      set of zinc fingers and downregulates its expression. Many studies have shown 
      that the primary role of SLUG during EMT and EMT-like processes is the regulation 
      of cell motility in most of the cancer cells. Knockdown of EVI1 in metastatic 
      colon cancer cell and subsequent passage through matrigel not only increased the 
      invading capacity but also induced an EMT-like morphological feature of the 
      cells, such as spindle-shaped appearance and led to a significant reduction in 
      the expression of the epithelial marker, E-CADHERIN and increase in the 
      expression of the mesenchymal marker, N-CADHERIN. The cells, when injected into 
      immunocompromised mice, failed to show any metastatic foci in distant organs 
      however the ones with EVI1, metastasized in the intraperitoneal layer and also 
      showed multiple micro metastatic foci in the lungs and spleen. These findings 
      suggest that in colon cancer EVI1 is dispensable for epithelial-mesenchymal 
      transition, however, is required for metastasis.
FAU - Nayak, Kasturi Bala
AU  - Nayak KB
AD  - Department of Gene Function and Regulation, Institute of Life Sciences Nalco 
      Square, Bhubaneswar, Odisha, India.
FAU - Sajitha, I S
AU  - Sajitha IS
AD  - Department of Veterinary Pathology, College of Veterinary & Animal Sciences, 
      Wayanad, Kerala, India.
FAU - Kumar, T R Santhosh
AU  - Kumar TRS
AD  - Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
FAU - Chakraborty, Soumen
AU  - Chakraborty S
AD  - Department of Gene Function and Regulation, Institute of Life Sciences Nalco 
      Square, Bhubaneswar, Odisha, India. soumen@ils.res.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180116
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MDS1 and EVI1 Complex Locus Protein)
RN  - 0 (MECOM protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Snail Family Transcription Factors)
SB  - IM
MH  - Base Sequence
MH  - Biomarkers, Tumor/metabolism
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/genetics/*pathology
MH  - Down-Regulation/genetics
MH  - *Epithelial-Mesenchymal Transition/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - MDS1 and EVI1 Complex Locus Protein/genetics/*metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - Snail Family Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic
PMC - PMC5833819
COIS- The authors declare that they have no competing financial interests.
EDAT- 2018/01/18 06:00
MHDA- 2019/06/18 06:00
PMCR- 2018/01/16
CRDT- 2018/01/18 06:00
PHST- 2017/03/29 00:00 [received]
PHST- 2017/10/09 00:00 [accepted]
PHST- 2017/10/08 00:00 [revised]
PHST- 2018/01/18 06:00 [entrez]
PHST- 2018/01/18 06:00 [pubmed]
PHST- 2019/06/18 06:00 [medline]
PHST- 2018/01/16 00:00 [pmc-release]
AID - 10.1038/s41419-017-0036-1 [pii]
AID - 36 [pii]
AID - 10.1038/s41419-017-0036-1 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Jan 16;9(2):18. doi: 10.1038/s41419-017-0036-1.