Search

Lirui He, Yunpeng Lei, Jianing Hou, Jianlong Wu, Guoqing Lv Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, People’s Republic of ChinaCorrespondence: Guoqing LvPeking University Shenzhen Hospital, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong 518000, People’s Republic of ChinaEmail GuoqingLv123@126.comBackground: Gastric cancer (GC) is an aggressive malignancy with high lethality. Systematic chemotherapy is the main therapeutic strategy for advanced GC patients. The overexpression of Axl is associated with poor prognosis and regulates tumor growth and metastasis in many types of cancer. However, the role of Axl in GC progression remains elusive.Materials and Methods: Western blot and quantitative real-time PCR assay (RT-PCR) assays were used to detect the expression of Gas6, Axl, ZEB1 and epithelial-mesenchymal transition (EMT)-related markers in GC cells. Cell proliferation was determined by EdU cell proliferation assay and CCK-8 assay. Transwell invasion assay was performed to explore the effect of Axl and ZEB1 on cell invasion. Tumor xenografts and lung metastasis models were conducted to examine the effect of Axl on the growth and lung metastasis of GC cells.Results: In our study, we found that high levels of Gas6 and Axl expression were associated with reduced overall survival (OS) in GC patients and the expression of Gas6 and Axl was upregulated in GC cell lines. Ectopic expression of Axl induced EMT and promoted GC cell invasion and proliferation. The knockdown of Axl inhibited EMT and suppressed the proliferation and invasion of GC cell. In vivo study showed that inhibition of Axl impaired tumor growth and lung metastasis of GC cells. Mechanistic investigations revealed that Axl promoted EMT, invasion, and proliferation via upregulating ZEB1 expression in GC cells.Conclusion: Our results demonstrated that the Gas6/Axl/ZEB1 signaling pathway regulated EMT, invasion, and proliferation in GC cells and might represent a potential therapeutic target for GC treatment.Keywords: gastric cancer, Gas6/Axl signaling pathway, ZEB1, EMT, invasion, proliferation

Boran Cheng,1,* Gangling Tong,1,* Xuan Wu,1,* Wenwu Cai,2,* Zhu Li,1,* Zhongyi Tong,2 Lirui He,1 Shaokang Yu,1 Shubin Wang1 1Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province 518036, People’s Republic of China; 2Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Boran Cheng; Shubin WangDepartment of Oncology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong Province 518036, People’s Republic of ChinaTel +86 755 135-3093-5356Fax +86 755-8392-3333Email BRcheng@whu.edu.cn; Shubinwang@aliyun.comBackground: Advanced gastric cancer (aGC) has a high global incidence and a high mortality rate and because of its high malignancy and heterogeneity, the existing methods for prognosis are limited, and a new treatment model is necessary. Circulating tumor cells (CTCs) could be considered as a “liquid biopsy” for tumor diagnosis and for monitoring treatment responses and predicting clinical outcome. Clinical studies support the efficacy of programmed cell death 1 (PD-1) immunotherapy in a subset of aGC.Methods: Cell capture efficiency, as described by the CanPatrol CTC enrichment technique, was validated using artificial blood samples as well as blood samples from 32 aGC patients. Clinicopathologic data of patients were collected from the hospital information system. We used CanPatrol for CTC isolation, classification, and clinical analysis.Results: A cell capture efficiency of >80% was achieved. Significant correlation was observed between CTC enumeration and clinicopathology parameters, including the Lauren classification (r=0.470, P=0.008), perineural invasion (r=0.393, P=0.029), TNM stage (r=0.740, P