Effect And Action Mechanism Of Syntaxin6 (STX6) In Occurrence And Development Of Esophageal Squamous Cell Carcinoma

Objective:To investigate the role of STX6 in esophageal squamous cell carcinoma growth and migration.Methods:To explore the effect and action mechanism of syntaxin 6"(STX6) in occurrence and development of esophageal cancer, clinical data of 216 patients with esophageal cancer were retrospectively studied by analyzing the relationships between the expression of STX6 and the clinical parameters. STX6 gene silencing was established by inhibiting RNA in human esophageal cancer cell lines ECA109 and TE1 cells and the significant silencing effect was validated by immunohistochemistry and immunoblotting analysis. The effect of inhibition of STX6 on the viability, growth rate, cycle and capability of migration of human esophageal cancer cell lines ECA109 and TE1 cells was investigated using MTT, colony-forming assay, cell cycle analysis, wound healing assay and in vitro migration assays. The change of P53 level was detected after inhibition of STX6 and the regulation of P53 on STX6 was investigated by inhibiting the expression of P53 in ECA109 and TE1 cells with STX6 silencing. Furthermore, the effect of STX6 silencing on distribution of integrin in cell was determined using flow cytometry and immunofluorescence assay to elucidate the action mechanism of STX6 on cell migration.Results:In the study, STX6 was overexpressed in the clinical samples of esophageal squamous cell carcinoma (ESCC), which level was significantly higher in the tumor tissues of esophageal cancer than that in normal tissues, suggesting that STX6 may play an important role in occurrence and development of esophageal cancer. STX6 expression was significantly correlated with tumor size, histological differentiation, lymph node metastasis and depth, but not associated with age or gender. Collectively, these data suggested that STX6 might function as a driver in the progression of ESCC. STX6 silencing inhibited the viability and proliferation of ESCC cells, since growth rate and survival of cells obviously decreased, migration weakened, percentage of G0/G1 phases increased and S phase was suppressed in a cell cycle after inhibition of STX6, a proto-oncogene. STX6 silencing induced ESCC cells growth suppression is P53 dependent, which protein level increased after inhibition of STX6. Partial characteristics disappearing after inhibition of STX6 were recovered by inhibiting P53 protein, suggesting the regulation of STX6 is P53 dependent. STX6 silencing inhibited ESCC cells migration and affected integrin trafficking in ESCC cells migration by regulating the trafficking of integrin, since integrin decreased on cell surface and mostly existed in nucleus and cytoplasm after inhibition of STX6, revealing some mechanism of weakened cell migration after inhibition of STX6.Conclusion:We we have found that the expression of STX6 was up-regulated in ESCC samples, its expression was significantly correlated with tumor size, histological differentiation, lymph node metastasis and depth. On one hand, STX6 silencing inhibited ESCC cells viability and proliferation in a P53-dependent manner. On the other hand, STX6 effect integrin trafficking and regulate ESCC cells migration. Taken together, our study revealed the oncogenic roles of STX6 in the progression of ESCC, and it might be a valuable target for ESCC therapy.