虽然累积的证据已经突出显示了hTERT促进肿瘤细胞入侵和转移的分子机制，但启用hTERT促进入侵和转移的属性的分子机制尚未清楚说明。在这里，我们报道了hTERT通过招募p50协同抑制PLEKHA7表达促进胃癌侵袭和转移。我们观察到胃癌中PLEKHA7的表达与TNM分期和淋巴转移显著负相关，而PLEKHA7表达的下降显著增加了胃癌细胞的侵袭和转移。进一步的机制研究表明，hTERT通过结合p50并招募hTERT/p50复合物到PLEKHA7启动子直接调节PLEKHA7的表达。增加hTERT显著降低PLEKHA7的表达并促进胃癌细胞的侵袭和转移。hTERT介导的侵袭/转移特性至少部分取决于PLEKHA7。我们的工作揭示了由hTERT和p50协调组织的胃癌侵袭/转移的新分子机制。©2023作者。

Although accumulating evidence has highlighted the molecular mechanisms by which hTERT promotes tumour cell invasion and metastasis, the molecular mechanisms of the properties enabling hTERT to contribute to invasion and metastasis have not been clearly illustrated. Here, we report that hTERT promotes gastric cancer invasion and metastasis by recruiting p50 to synergistically inhibit PLEKHA7 expression. We observed that the expression of PLEKHA7 in gastric cancer was significantly negatively associated with the TNM stage and lymphatic metastasis and that decreased PLEKHA7 expression dramatically increased invasion and metastasis in gastric cancer cells. Further mechanistic research showed that hTERT directly regulates PLEKHA7 expression by binding p50 and recruiting the hTERT/p50 complex to the PLEKHA7 promoter. Increased hTERT dramatically decreased PLEKHA7 expression and promoted invasion and metastasis in gastric cancer cells. The hTERT-mediated invasion/metastasis properties at least partially depended on PLEKHA7. Our work uncovers a novel molecular mechanism underlying invasion/metastasis in gastric cancer orchestrated by hTERT and p50.© 2023. The Author(s).