Human telomerase reverse transcriptase (hTERT) synergistic with Sp1 upregulate Gli1 expression and increase gastric cancer invasion and metastasis.

Abstract

Abnormal expression of human telomerase reverse transcriptase (hTERT) has been widely identified in tumors, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism ofhTERTin gastric cancer metastasis. Gastric cancer and adjacent non-tumor tissues were collected and the expression levels of hTERT and Gli1 were detected by immunohistochemistry. The results demonstrated that hTERT and Gli1 expression levels in gastric cancer tissue were significantly higher than adjacent non-tumor tissues. Western blot and quantitative real-time PCR were used to an identified expression of the related protein in BGC-823 and SGC-7901 cells. The interactions betweenhTERTandSp1were tested by co-immunoprecipitation experiments. Chromatin immunoprecipitation was performed to confirm thatSp1andhTERTcould bind to theGli1promoter. Chromatin reimmunoprecipitation assay further demonstrated that bothhTERTandSp1bind to theSp1site of theGli1promoter. Moreover, thehTERT,Sp1, andGli1were upregulate was verified in human gastric cancer tissues. These results showed that the expression levels ofhTERTin GC tissues were strongly closed to the depth of invasion, lymph node metastasis, TNM (tumor, node, metastasis) stage, and distant metastasis. By combiningSp1andGli1promoter,hTERTupregulatedGli1expression and promoted invasion and metastasis of GC cells. Overall, these data provide a new molecular mechanism ofhTERTto promotes gastric cancer progression. Targetingthe hTERT/Sp1/Gli1axis may represent a new therapeutic strategy.