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http://purl.uniprot.org/citations/30556860http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30556860http://www.w3.org/2000/01/rdf-schema#comment"

Objective

This study aimed to characterize the effect of Twist2 on epithelial-to-mesenchymal transition (EMT) and the invasive potential of colorectal cancer (CRC) cells and to explore the mechanisms underlying the regulative effect of Twist1 and Twist2 on matrix metalloproteinase 2 (MMP2) expression in CRC.

Patients and methods

Data mining was performed in colorectal cancer cohort (COADREAD) in the Cancer Genome Atlas (TCGA-COADREAD). CRC LoVo and HCT116 cells were used as in vitro cell models.

Results

CRC tumors with lymphatic invasion (N = 102) had a significantly higher expression of TWIST1 (p = 0.01) and TWIST2 (p = 0.02) than the lymphatic invasion negative cases (N = 228). TWIST2 overexpression enhanced EMT and the invasive potential of the CRC LoVo and HCT116 cells, while TWIST2 knockdown reversed the EMT process and weakened the invasive potential of the cells. TWIST1 and TWIST2 were co-upregulated with MMP2 and MMP9 in COADREAD cohort. TWIST1 or TWIST2 overexpression significantly elevated nuclear β-catenin accumulation, which is a known signaling pathway elevating MMP2 and MMP9 expression. More importantly, we found that both Twist1 and Twist2 could transcriptionally activate MMP2 via directly binding to its promoter. However, this mechanism was not observed in the MMP9 promoter.

Conclusions

TWIST1/2 is associated with lymphatic invasion in CRC. TWIST2 upregulation enhances EMT and the invasive potential of CRC cells. TWIST1/2 can enhance the Wnt/β-catenin signaling pathway in CRC cells. In addition, Twist1/2 can bind to the MMP2 promoter and promote its transcription."xsd:string
http://purl.uniprot.org/citations/30556860http://purl.org/dc/terms/identifier"doi:10.26355/eurrev_201812_16514"xsd:string
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/author"Lu K."xsd:string
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/author"Dong J.L."xsd:string
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/author"Fan W.J."xsd:string
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/name"Eur Rev Med Pharmacol Sci"xsd:string
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/pages"8210-8219"xsd:string
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/title"Twist1/2 activates MMP2 expression via binding to its promoter in colorectal cancer."xsd:string
http://purl.uniprot.org/citations/30556860http://purl.uniprot.org/core/volume"22"xsd:string
http://purl.uniprot.org/citations/30556860http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/30556860
http://purl.uniprot.org/citations/30556860http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/30556860
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http://purl.uniprot.org/uniprot/P08253http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30556860
http://purl.uniprot.org/uniprot/Q15672http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30556860
http://purl.uniprot.org/uniprot/Q2EF79http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30556860
http://purl.uniprot.org/uniprot/Q8WVJ9http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30556860