TGF-β1-SOX9 axis-inducible COL10A1 promotes invasion and metastasis in gastric cancer via epithelial-to-mesenchymal transition

Cell Death & Disease
Tingting LiGuoxin Li

Abstract

Molecular biomarkers that predict disease progression might promote drug development and therapeutic strategies in aggressive cancers, such as gastric cancer (GC). High-throughput mRNA sequencing (RNA-seq) revealed that collagen type X alpha 1 (COL10A1) is a disease progression-associated gene. Analysis of 103 GC patients showed that high COL10A1 mRNA expression was associated with GC metastasis and reduced survival. We analyzed the COL10A1 promoter using the UCSC genome website and JASPAR database, and we found potential SOX9 binding site. Here, we demonstrated that SOX9 and COL10A1 were both up-regulated in GC. We observed a positive correlation between the expression patterns of SOX9 and COL10A1 in GC cells and tissues. The results of electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay and promoter reporter indicated that SOX9 could directly bind to the COL10A1 gene promoter and activate its transcription. Biological function experiments showed that COL10A1 regulated the migration and invasion of GC cells. Knockdown COL10A1 inhibited lung and abdominal cavity metastasis in a nude mouse model. Moreover, transforming growth factor-β1 (TGF-β1) treatment up-regulated the phosphorylation of Sma...Continue Reading

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Datasets Mentioned

BETA
SGC7901

Methods Mentioned

BETA
RNA-req
surgical resection
RNA-seq
transfection
ChIP
electrophoretic mobility shift
immunoprecipitation
RNAseq
Illumina sequencing
PCR

Software Mentioned

Cuffdiff
ImageJ
NIH ImageJ
Cufflinks
SPSS

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