PMID- 30426548
OWN - NLM
STAT- MEDLINE
DCOM- 20200708
LR  - 20220408
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 4
DP  - 2019 Apr
TI  - Knockdown GREM1 suppresses cell growth, angiogenesis, and epithelial-mesenchymal 
      transition in colon cancer.
PG  - 5583-5596
LID - 10.1002/jcb.27842 [doi]
AB  - Gremlin 1 (GREM1), as a bone morphogenetic protein (BMP) antagonist and vascular 
      endothelial growth factor receptor-2 (VEGFR2) novel agonist, has been confirmed 
      as overexpressed in colorectal cancer (CRC) tissues but its role in 
      carcinogenesis remains unclear. Here we reported that the GREM1 expression in 
      mesenchymal-like colon cancer cells (SW620 and SW480) was significantly higher 
      than that of epithelial-like colon cancer cells (Caco-2, HTC116, and HT29) and 
      normal colon cell. Simultaneously, we analyzed two series of CRC transcriptomes 
      from Gene Expression Omnibus (GEO) databases and found the great majority of 
      primary CRC tissues expressed high level of GREM1 messenger RNA (mRNA) compared 
      with adjacent normal tissues, and that the GREM1 mRNA expression is correlated 
      with low histological grade development and stage 2 to 3 metastatic recurrence in 
      CRC based on a data analysis of 104 different stage CRC tissue from the GEO 
      databases. Functional studies showed that GREM1 silencing by short hairpin RNA 
      (shRNA) significantly inhibited CRC cells proliferation, migration, the formation 
      of vascular endothelial growth factor (VEGF)-induced capillary structure of human 
      umbilical vein endothelial cells (HUVECs), and epithelial-mesenchymal transition 
      in colon cancer cells by repressing phosphorylation levels of BMP downstream 
      signal Smad1, vascular endothelial growth factor (VEGF) downstream signal matrix 
      metallopeptidase 2 (MMP2), and metastasis-related factor C-X-C motif chemokine 
      ligand 12 (CXCL12) expression. In addition, shGREM1 combined with VEGF inhibitor 
      BAW2881 displayed more effective antiangiogenesis to inhibit the tube formation 
      of HUVEC. Hence, these experiments demonstrated that GREM1 is involved in CRC 
      development and procession and provide a new idea for CRC diagnosis, resistance 
      therapy, and prognosis.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Liu, Yan
AU  - Liu Y
AD  - Department of Ultrasonography, China-Japan Union Hospital, Jilin University, 
      Changchun, China.
FAU - Li, Yongchao
AU  - Li Y
AD  - Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union 
      Hospital, Jilin University, Changchun, China.
FAU - Hou, Ruizhe
AU  - Hou R
AD  - Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital, 
      Jilin University, Changchun, China.
AD  - Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital, 
      Jilin University, Changchun, China.
FAU - Shu, Zhenbo
AU  - Shu Z
AUID- ORCID: 0000-0003-3851-3074
AD  - Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union 
      Hospital, Jilin University, Changchun, China.
AD  - Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital, 
      Jilin University, Changchun, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181113
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (GREM1 protein, human)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Caco-2 Cells
MH  - Colonic Neoplasms/genetics/*metabolism/pathology
MH  - *Epithelial-Mesenchymal Transition
MH  - Gene Knockdown Techniques
MH  - HCT116 Cells
MH  - HT29 Cells
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Neovascularization, Pathologic/genetics/*metabolism
OTO - NOTNLM
OT  - colon cancer
OT  - epithelial-mesenchymal transition
OT  - gremlin 1
OT  - metastasis
OT  - proliferation
EDAT- 2018/11/15 06:00
MHDA- 2020/07/09 06:00
CRDT- 2018/11/15 06:00
PHST- 2018/03/12 00:00 [received]
PHST- 2018/09/14 00:00 [accepted]
PHST- 2018/11/15 06:00 [pubmed]
PHST- 2020/07/09 06:00 [medline]
PHST- 2018/11/15 06:00 [entrez]
AID - 10.1002/jcb.27842 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Apr;120(4):5583-5596. doi: 10.1002/jcb.27842. Epub 2018 Nov 
      13.