L-Plastin Promotes Gastric Cancer Growth and Metastasis in a Helicobacter pylori cagA -ERK-SP1–Dependent Manner

作者：Yong‐sheng Teng, Wan‐Yan Chen, Zong‐Bao Yan, Yi-pin Lv, Yugang Liu, Fangyuan Mao, Yongliang Zhao, Liu‐sheng Peng, Ping Cheng, Mubing Duan, Weisan Chen, Yu Wang, Ping Luo, Quanming Zou, Jun Chen, Yuan Zhuang · 发表于：Molecular Cancer Research · 年份：2021 · DOI：10.1158/1541-7786.mcr-20-0936 · 被引用次数：9 · 研究领域：Helicobacter pylori-related gastroenterology studies、Galectins and Cancer Biology、Veterinary medicine and infectious diseases

Abstract Actin cytoskeleton dynamic rearrangement is required for tumor cell metastasis and is a key characteristic of Helicobacter pylori (H. pylori)-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 H. pylori infection significantly induced L-plastin, a key ABP, in gastric cancer cells. We further explored the regulation and function of L-plastin in H. pylori–associated gastric cancer and found that, mechanistically, H. pylori infection induced gastric cancer cells to express L-plastin via cagA-activated ERK signaling pathway to mediate SP1 binding to L-plastin promoter. Moreover, this increased L-plastin promoted gastric cancer cell proliferation and migration in vitro and facilitated the growth and metastasis of gastric cancer in vivo. 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 cagA+ H. pylori infection status. Overall, our results elucidate a novel mechanism of L-plastin expression induced by H. pylori, 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-plast...