<p>C-terminal of E1A binding protein 1 enhances the migration of gastric epithelial cells and has a clinicopathologic significance in human gastric carcinoma</p>

Abstract

Background Recent studies have claimed that the C-terminal of E1A binding proteins (CtBPs) influence tumorigenesis through participating in cell signal transduction in various human tumors. However, the detailed expression profiles of CtBP isoforms in human gastric cancer (GC) and the molecular mechanisms of CtBP involvement in tumor cell phenotypes warrant further investigation. Materials and methods The expression of CtBPs in GC cell lines and a human gastric epithelial cell line were explored via RT-qPCR and Western blotting assays. Moreover, the expression profiles of CtBPs in GC and histologically noncancerous tissues were explored by immunohistochemistry. To explore the effects of CtBP1 on the metastatic phenotype in GC, gastric epithelial cells were transfected with a eukaryotic expression plasmid to overexpress CTBP1, and the endogenous CtBP1 or JAK1 in GC cells was silenced through an RNA interference (RNAi) method. These transfections were validated via Western blotting, and the activation state of the JAK1/Stat3 signaling pathway was also explored via Western blotting. Furthermore, the malignant phenotype of GC cells was evaluated via a Cell Counting Kit-8 (CCK8) assay, colony formation assay, transwell assay, and wound-healing experiment. Results Our data revealed that the expression of CtBP1, but not CTBP2, was upregulated in 102 GC tissue samples compared with 98 noncancerous tissue samples, and the elevated expression level of CtBP1 was notably associated with distant metastasis. CTBP1 modulated cell migration and invasion through the JAK1/Stat3 signaling pathway in gastric epithelial cells. In addition, genetic silence of CtBP1 expression in GC cells notably constrained cell proliferation, invasion and migration abilities through inhibiting the activation of the JAK1/Stat3 pathway in GC cells. Conclusion Our data reveal that the knockout of CtBP1 notably constrains distant metastasis in GC through the JAK1/Stat3 pathway, suggesting that targeting CtBP1 is a practical anti-tumor approach to restrain tumor progression in GC.

Propofol Stimulates Immune Activity and Decreases Inflammatory Cytokines via NF-κB-Mediated JAK1-STAT3 Pathway in Gastric Cancer Patients Undergoing Radical Surgery

“…Chen et al found that activation of JAK1/STAT3 signaling inhibited tumorigenesis and induced cell apoptosis repression in gastric cancer (48). Notably, inhibiting the activation of the JAK1/Stat3 pathway is a practical anti-tumor approach to restrain tumor progression in in gastric cancer (49). The present study also reported that propofol regulated immune function via the NF-κB-mediated JAK1/STAT3 signaling pathway in gastric cancer cells.…”

NAD(H) phosphates mediate tetramer assembly of human C-terminal binding protein (CtBP)

“…Substantial evidence ( 4 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ) suggests that CtBP may be a useful target for antineoplastic agents. Application of structure-based drug design approaches requires a detailed understanding of cotranscriptional activation, which for CtBP includes defining the trigger for tetramer formation.…”

“…Consistent with a role in repression of apoptotic pathways and activation of growth and metastasis, CtBP is upregulated in a number of cancer tissues including colorectal cancer ( 15 ), melanoma ( 16 ), metastatic prostate cancer ( 17 ), esophageal squamous cell carcinoma ( 18 ), ovarian cancer ( 19 ), and breast cancer ( 20 , 21 ). Strikingly, elevated levels of CtBP in tumor tissue have been correlated with poorer survival in breast cancer ( 22 ), ovarian cancer ( 19 ), gastric carcinoma ( 23 ), and hepatocellular carcinoma ( 24 ). Recent results add to evidence of a link between CtBP and cancer progression by showing increased survival in mice models for colon cancer ( APC min/+ ) ( 25 ) and pancreatic adenocarcinoma (CKP) ( 26 ) when CtBP2 levels are lowered by CtBP2 +/- heterozygosity.…”

CTBP1 strengthens the cisplatin resistance of gastric cancer cells by upregulating RAD51 expression

“…Furthermore, during the development of gastric cancer, microRNA (miR)-539-3p inhibits the migration and invasion of gastric tumor cells by suppressing CTBP1 expression ( 15 ). Notably, high levels of CTBP1 can also promote the proliferation, migration and invasion of gastric tumor cells ( 16 ). Importantly, CTBP1 is reported to confer DDP resistance to breast cancer cells ( 17 ).…”