2. Academic Validation
  3. ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer

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

  • Cell Death Dis. 2023 Feb 15;14(2):124. doi: 10.1038/s41419-023-05648-9.
Wangkai Xie # 1 2 3,  Zheng Han # 1 2 3,  Ziyi Zuo # 2 3,  Dong Xin # 3,  Hua Chen 2 3,  Juanjuan Huang 3,  Siyu Zhu 3,  Han Lou 3,  Zhiqiang Yu 1 2 3,  Chenbin Chen 1 2 3,  Sian Chen 4,  Yuanbo Hu 1 2 3,  Jingjing Huang 5,  Fabiao Zhang 6,  Zhonglin Ni 1,  Xian Shen 7 8 9,  Xiangyang Xue 10 11,  Kezhi Lin 12
Affiliations

Affiliations

  • 1 Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Experiemtial Center of Basic Medicine, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
  • 4 Department of emergency, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5 Department of Pathology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 6 Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Department of Hepatic-biliary-pancreatic Surgery Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 317000, Zheiang Province, Linhai, China.
  • 7 Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • 8 Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • 9 Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Experiemtial Center of Basic Medicine, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. [email protected].
  • 10 Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • 11 Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Experiemtial Center of Basic Medicine, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. [email protected].
  • 12 Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Experiemtial Center of Basic Medicine, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. [email protected].
  • # Contributed equally.
PMID: 36792578 DOI: 10.1038/s41419-023-05648-9
Abstract

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.

Figures
Products