Blockade of CXCR6 reduces invasive potential of gastric cancer cells through inhibition of AKT signaling.
Chemokines and their receptors have been implicated in cell migration and metastasis of multiple malignant tumors. But the function of CXCR6 signaling in gastric cancer is not comprehensively understood. In the present study, we hypothesized that CXCR6 signaling might play an essential role in the progression of gastric cancer. The expression of CXCR6 was examined by immunohistochemical assay in human gastric cancer, and lentivirus-mediated CXCR6 knockdown by shRNA (Lv-shCXCR6) was used for investigating cell migration and invasion indicated by Wound-healing and Transwell assays. Consequently, the expression level of CXCR6 was increased in gastric cancer compared with the adjacent non-tumor tissues (54.2% vs. 27.1%, P = 0.006), and was closely associated with the metastatic lymph node in gastric cancer (P = 0.021). Furthermore, blockade of the CXCR6 signaling reduced the migration and invasion of gastric cancer cells followed by decreased expression of AKT, MMP-2, and MMP-9. In conclusion, these findings demonstrate that CXCR6 may promote the development of gastric cancer cells through regulation of AKT signaling.
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
Ya
Y
Li
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
Li-Xia
LX
Fu
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
Wan-Lin
WL
Zhu
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
Hua
H
Shi
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China.
Li-Jian
LJ
Chen
Department of Gastroenterology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, PR China yebin20152@163.com.
Bin
B
Ye
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011991:Receptors, Virus / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents; C106330:CXCR6 protein, human; D034741:RNA, Small Interfering; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
AKT; CXCR6; gastric cancer; invasion