National Engineering Research Centre of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Third Military Medical University, Chongqing, P.R. China.
Department of General Surgery and Centre of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.
Mol Cancer Res. 2021 Jun;19(6):968-978. doi: 10.1158/1541-7786.MCR-20-0936. Epub 2021 Mar 26.
Actin cytoskeleton dynamic rearrangement is required for tumor cell metastasis and is a key characteristic of ()-infected host cells. Actin cytoskeleton modulation is coordinated by multiple actin-binding proteins (ABP). Through Kyoto encyclopedia of gene and genomes database, GEPIA website, and real-time PCR data, we found that infection significantly induced L-plastin, a key ABP, in gastric cancer cells. We further explored the regulation and function of L-plastin in -associated gastric cancer and found that, mechanistically, infection induced gastric cancer cells to express L-plastin via -activated ERK signaling pathway to mediate SP1 binding to L-plastin promoter. Moreover, this increased L-plastin promoted gastric cancer cell proliferation and migration and facilitated the growth and metastasis of gastric cancer . Finally, we detected the expression pattern of L-plastin in gastric cancer tissues, and found that L-plastin was increased in gastric cancer tissues and that this increase of L-plastin positively correlated with infection status. Overall, our results elucidate a novel mechanism of L-plastin expression induced by , and a new function of L-plastin-facilitated growth and metastasis of gastric cancer, and thereby implicating L-plastin as a potential therapeutic target against gastric cancer. IMPLICATIONS: Our results elucidate a novel mechanism of L-plastin expression induced by in gastric cancer, and a new function of L-plastin-facilitated gastric cancer growth and metastasis, implicating L-plastin as a potential therapeutic target against gastric cancer.
肌动蛋白细胞骨架的动态重排是肿瘤细胞转移所必需的，也是感染宿主细胞的关键特征。肌动蛋白细胞骨架的调节是由多种肌动蛋白结合蛋白（ABP）协调的。通过京都基因与基因组百科全书数据库、GEPIA 网站和实时 PCR 数据，我们发现感染显著诱导了胃癌细胞中的关键 ABP——L 型肌动蛋白。我们进一步探讨了 L 型肌动蛋白在相关胃癌中的调节和功能，发现从机制上讲，感染通过激活 ERK 信号通路诱导胃癌细胞表达 L 型肌动蛋白，从而介导 SP1 与 L 型肌动蛋白启动子结合。此外，这种增加的 L 型肌动蛋白促进了胃癌细胞的增殖和迁移，并促进了胃癌的生长和转移。最后，我们检测了胃癌组织中 L 型肌动蛋白的表达模式，发现胃癌组织中 L 型肌动蛋白增加，并且这种 L 型肌动蛋白的增加与感染状况呈正相关。总的来说，我们的研究结果阐明了感染诱导 L 型肌动蛋白表达的新机制，以及 L 型肌动蛋白促进胃癌生长和转移的新功能，从而暗示 L 型肌动蛋白作为一种治疗胃癌的潜在靶点。
我们的研究结果阐明了感染在胃癌中诱导 L 型肌动蛋白表达的新机制，以及 L 型肌动蛋白促进胃癌生长和转移的新功能，从而暗示 L 型肌动蛋白作为一种治疗胃癌的潜在靶点。
