机构:[1]Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China外科科室胃肠外科中山大学附属第一医院[2]Gastric Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, China[3]Gastrointestinal Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China外科科室胃肠外科中山大学附属第一医院[4]Indiana University School of Medicine, South Bend, and IU Health Goshen Center for Cancer Care, Goshen, IN, USA[5]Division of Surgical Oncology, Department of Surgery, and the Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples. CXCR4 and CXCR2 were highly expressed in a high invasive gastric cancer cell model and in gastric cancer tissues. Overexpression of CXCR4 and CXCR2 was associated with more advanced tumor stage and poorer survival for GC patients. CXCR4 and CXCR2 expression strongly correlated with each other in the way that CXCR2 expression changed accordingly with the activity of CXCR4 signaling and CXCR4 expression also changed in agreement with CXCR2 activity. Further studies demonstrated CXCR4 and CXCR2 can both activated NF-kappa B and STAT3 signaling, while NF-kappa Bp65 can then transcriptionally activate CXCR4 and STAT3 can activate CXCR2 expression. This crosstalk between CXCR4 and CXCR2 contributed to EMT, migration and invasion of gastric cancer. Finally, Co-inhibition of CXCR4 and CXCR2 is more effective in reducing gastric cancer metastasis. Our results demonstrated that CXCR4 and CXCR2 cross-activate each other to promote the metastasis of gastric cancer.
基金:
National Natural Science Foundation of China [81272643, 81272637]; '3 & 3' project of The First Affiliated Hospital of Sun Yat-sen University
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类|1 区医学
小类|1 区遗传学2 区生化与分子生物学2 区细胞生物学2 区肿瘤学
最新[2023]版:
大类|1 区医学
小类|1 区生化与分子生物学1 区遗传学2 区细胞生物学2 区肿瘤学
第一作者:
第一作者机构:[1]Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China[2]Gastric Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China[2]Gastric Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, China[*1]Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China.
推荐引用方式(GB/T 7714):
Z Xiang,Z-J Zhou,G-K Xia,et al.A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis[J].ONCOGENE.2017,36(36):5122-5133.doi:10.1038/onc.2017.108.
APA:
Z Xiang,Z-J Zhou,G-K Xia,X-H Zhang,Z-W Wei...&C-H Zhang.(2017).A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis.ONCOGENE,36,(36)
MLA:
Z Xiang,et al."A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis".ONCOGENE 36..36(2017):5122-5133