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端粒酶逆转录酶-p50 同源二聚体抑制 PLEKHA7 的表达，促进胃癌的侵袭和转移。

The hTERT-p50 homodimer inhibits PLEKHA7 expression to promote gastric cancer invasion and metastasis.

机构信息

Department of Gastroenterology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China.

Department of Endoscope, The General Hospital of Shenyang Military Region, Shenyang, 110016, China.

出版信息

Oncogene. 2023 Mar;42(14):1144-1156. doi: 10.1038/s41388-023-02630-9. Epub 2023 Feb 23.

DOI:10.1038/s41388-023-02630-9
PMID:36823376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10063444/
Abstract

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.

摘要

虽然越来越多的证据强调了端粒酶逆转录酶（hTERT）促进肿瘤细胞侵袭和转移的分子机制，但 hTERT 促进侵袭和转移的特性的分子机制尚不清楚。在这里，我们报告 hTERT 通过招募 p50 来协同抑制 PLEKHA7 的表达，从而促进胃癌的侵袭和转移。我们观察到，胃癌中 PLEKHA7 的表达与 TNM 分期和淋巴转移呈显著负相关，而 PLEKHA7 表达的降低则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 通过与 p50 结合直接调节 PLEKHA7 的表达，并募集 hTERT/p50 复合物到 PLEKHA7 启动子上。hTERT 的表达增加显著降低了 PLEKHA7 的表达，并促进了胃癌细胞的侵袭和转移。hTERT 介导的侵袭/转移特性至少部分依赖于 PLEKHA7。我们的工作揭示了 hTERT 和 p50 协调的胃癌侵袭/转移的新分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/e91a6fe7fa73/41388_2023_2630_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/1151204dcd25/41388_2023_2630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/6030870e408f/41388_2023_2630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/f9384e290536/41388_2023_2630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/cb2d405afe37/41388_2023_2630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/e2d770733174/41388_2023_2630_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/6414f05aa912/41388_2023_2630_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/4e4f4802c811/41388_2023_2630_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/e91a6fe7fa73/41388_2023_2630_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/1151204dcd25/41388_2023_2630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/6030870e408f/41388_2023_2630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/f9384e290536/41388_2023_2630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/cb2d405afe37/41388_2023_2630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/e2d770733174/41388_2023_2630_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/6414f05aa912/41388_2023_2630_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/4e4f4802c811/41388_2023_2630_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fa/10063444/e91a6fe7fa73/41388_2023_2630_Fig8_HTML.jpg

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