Inhibition of Ras protein activator like 2 produces antitumor effects in gastric cancer via the suppression of YAP1 activation

被引:3
|
作者
Hu, Yuan [1 ]
Zhang, Pengchuang [2 ]
Shi, Yu [1 ]
Dong, Xuyuan [1 ]
Wu, Yinying [1 ]
Dong, Danfeng [1 ]
Li, Enxiao [1 ]
Fan, Yangwei [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Med Oncol, Xian 710061, Shaanxi, Peoples R China
[2] Shaanxi Prov Tumor Hosp, Dept Gynecol Canc, Xian, Shaanxi, Peoples R China
关键词
gastric cancer; RASAL2; YAP1; CELL CONTACT INHIBITION; HIPPO PATHWAY; POOR-PROGNOSIS; EMERGING ROLE; METASTASIS; PROLIFERATION; TUMOR; EXPRESSION; INVASION;
D O I
10.1002/tox.23418
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Ras protein activator like 2 (RASAL2) has a cancer-related function, but plays inconsistent roles in different malignancies. This project was designed to determine the role of RASAL2 in carcinogenesis in gastric cancer. The Cancer Genome Atlas data revealed high levels of RASAL2 in gastric cancer tissue, which was confirmed in clinical specimens of gastric cancer via real-time quantitative PCR and western blotting assays. High RASAL2 was correlated with a reduced survival rate in gastric cancer patients. In gastric cancer cell lines, the silencing of RASAL2 restrained cellular proliferation, invasion and epithelial-to-mesenchymal transition, while enhancing chemosensitivity to cisplatin. Mechanistically, the silencing of RASAL2 was found to inhibit the activation of Yes-associated protein 1 (YAP1), a pro-oncogenic protein in gastric cancer, and decrease the expression of YAP1 target genes. The re-expression of constitutively active YAP1 substantially reversed RASAL2-silencing-produced antitumor effects. Moreover, treatment with YAP1 inhibitors could diminish RASAL2-overexpression-evoked oncogenic effects in gastric cancer cells. Additionally, gastric cancer cells with RASAL2 silencing exhibited a reduced ability to form xenograft tumors in nude mice. Collectively, our data demonstrate that the silencing of RASAL2 has noteworthy antitumor effects in gastric cancer cells via the suppression of YAP1 activation. This project underscores a vital role of the RASAL2/YAP1 axis in gastric progression and indicates that targeting this oncogenic axis may be applied as a potential therapeutic option for gastric cancer.
引用
收藏
页码:527 / 538
页数:12
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