ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer

被引:17
|
作者
Xie, Wangkai [1 ,2 ,3 ,4 ]
Han, Zheng [1 ,2 ,3 ,4 ]
Zuo, Ziyi [3 ,4 ]
Xin, Dong [4 ]
Chen, Hua [3 ,4 ]
Huang, Juanjuan [4 ]
Zhu, Siyu [4 ]
Lou, Han [4 ]
Yu, Zhiqiang [1 ,2 ,3 ,4 ]
Chen, Chenbin [1 ,2 ,3 ,4 ]
Chen, Sian [2 ,5 ]
Hu, Yuanbo [1 ,2 ,3 ,4 ]
Huang, Jingjing [2 ,6 ]
Zhang, Fabiao [7 ]
Ni, Zhonglin [1 ,2 ]
Shen, Xian [1 ,2 ,3 ,4 ]
Xue, Xiangyang [1 ,2 ,4 ]
Lin, Kezhi [4 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Gen Surg, Wenzhou, Peoples R China
[2] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 1, Dept Gen Surg, Wenzhou, Peoples R China
[4] Wenzhou Med Univ, Inst Mol Virol & Immunol, Sch Basic Med Sci, Dept Microbiol & Immunol,Experiemtial Ctr Basic Me, Wenzhou, Peoples R China
[5] Wenzhou Med Univ, Affiliated Hosp 2, Dept emergency, Wenzhou, Peoples R China
[6] Wenzhou Med Univ, Affiliated Hosp 2, Dept Pathol, Wenzhou, Peoples R China
[7] Wenzhou Med Univ, Taizhou Hosp, Dept Hepat biliary pancreat Surg, Key Lab Minimally Invas Tech & Rapid Rehabil Diges, Linhai 317000, Zheiang, Peoples R China
基金
中国国家自然科学基金;
关键词
POOR-PROGNOSIS; PROTEIN; CDC42; METASTASIS; EXPRESSION; SURVIVAL; EMT; PROLIFERATION; PHENOTYPE; CARCINOMA;
D O I
10.1038/s41419-023-05648-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.
引用
收藏
页数:16
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