Sex determining region Y-box 12 (SOX12) promotes gastric cancer metastasis by upregulating MMP7 and IGF1.
Metastasis is the major cause of poor survival and therapeutic failure in gastric cancer (GC). However, the molecular mechanisms underlying GC metastasis remain unclear. Here, we analyzed the expression patterns of sex determining region Y-box 12 (SOX12) in two independent cohorts of paired GC tissues and adjacent nontumor tissues and conducted in vitro and in vivo functional studies to determine the role of SOX12 in GC cells. High SOX12 expression in GC tissues was associated with increased frequency of recurrence and poorer patient survival. SOX12 overexpression increased GC cell migration, invasion and metastasis, whereas SOX12 downregulation decreased these behaviors. Reporter assays revealed that matrix metallopeptidase 7 (MMP7) and insulin-like growth factor 1 (IGF1) are transcriptional targets of SOX12 and indicated their requirement for SOX12-mediated GC metastasis. IGF1 induced SOX12 expression via the PI3K/AKT/CREB pathway, forming an IGF1/CREB/SOX12 feedback loop that contributed to GC metastasis. SOX12 expression correlated with MMP7 and IGF1 expression in GC tissues, and patients expressing SOX12 and either MMP7 or IGF1 had higher metastasis and recurrence rates and shorter survival than patients without that expression pattern. In conclusion, SOX12 is a novel prognostic biomarker and regulator of GC metastasis.
['Du|Feng|F|', 'Feng|Weibo|W|', 'Chen|Sheng|S|', 'Wu|Shengda|S|', 'Cao|Tianyu|T|', 'Yuan|Ting|T|', 'Tian|Dean|D|', 'Nie|Yongzhan|Y|', 'Wu|Kaichun|K|', 'Fan|Daiming|D|', 'Xia|Limin|L|']
D000818:Animals D014408:Biomarkers, Tumor D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D017362:Cyclic AMP Response Element-Binding Protein D058750:Epithelial-Mesenchymal Transition D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D007334:Insulin-Like Growth Factor I D008297:Male D020783:Matrix Metalloproteinase 7 D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D008875:Middle Aged D009361:Neoplasm Invasiveness D009362:Neoplasm Metastasis D058539:Phosphatidylinositol 3-Kinase D051057:Proto-Oncogene Proteins c-akt D034622:RNA Interference D034741:RNA, Small Interfering D055751:SOXC Transcription Factors D013274:Stomach Neoplasms D015854:Up-Regulation
SOX12 Gastric cancer Metastasis MMP7 IGF1