单位：[a]Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom[b]China-Japan Friendship Hospital, Yinghuayuan East Street, Beijing, 10029, China[c]Department of Pharmacy, Southern University of Science and Technology Hospital, Shenzhen, 518055, China深圳市康宁医院深圳医学信息中心[d]Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China临床科室国家中心普外分中心普外五科（综合普外科）首都医科大学附属北京友谊医院[e]Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China临床科室肿瘤中心首都医科大学附属北京友谊医院[f]Key Laboratory of Carcinogenesis and Translational Research, Department of GI Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China
Background S100A11 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. The dysregulated expression of the S100A11 gene has been implicated in tumour metastasis. However, the role of S100A11 protein in tumour cell response to chemotherapeutic drugs has not been characterised. Methods Transcript levels of S100A11 in gastric cancer were evaluated using an in-house patient cohort. Protein expression of S100A11 in gastric cancer was estimated by immunohistochemistry of a tissue microarray. The stable gastric cancer cell lines were established using lentiviral shRNA vectors. The knockdown of S100A11 was validated by qRT-PCR, PCR, and Western blot. The cellular function of S100A11 was estimated by assays of cell adhesion, migration, and invasion. The cell cytotoxic assay was performed to investigate the response to chemotherapeutic drugs. An unsupervised hierarchical clustering and principal component analysis (HCPC) was applied to unveil the dimensional role of S100A11 among all S100 family members in gastric cancer. Results High expression of S100A11 is associated with poor survival of gastric cancer patients (p < 0.001, HR = 1.85) and is an independent prognostic factor of gastric cancer. We demonstrate that S100A11 plays its role as a tumour promoter through regulating the MMP activity and the epithelial-mesenchymal transition (EMT) process. The stable knockdown of S100A11 suppresses the metastatic properties of gastric cancer cells, which include enhancing cell adhesion, but decelerating cell migration and invasion. Furthermore, the knockdown of S100A11 gene expression dramatically induces the cellular response of gastric cancer cells to the first-line chemotherapeutic drugs fluoropyrimidine 5-fluorouracil (5-FU) and cisplatin. Conclusion The present study identifies S100A11 as a tumour promoter in gastric cancer. More importantly, the S100A11-specific targeting potentially presents dual therapeutic benefits by not only controlling tumour progression but also sensitising chemotherapeutic cytotoxic response.
第一作者单位：[a]Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom
通讯作者：
推荐引用方式(GB/T 7714)：
Cui Y,Li L,Li Z,et al.Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer[J].CANCER CELL INTERNATIONAL.2021,21(1):doi:10.1186/s12935-021-01949-1.
APA：
Cui, Y,Li, L,Li, Z,Yin, J,Lane, J...&Jiang, W.G.(2021).Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer.CANCER CELL INTERNATIONAL,21,(1)
MLA：
Cui, Y,et al."Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer".CANCER CELL INTERNATIONAL 21..1(2021)
