title: Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and β-arrestin pathways.
abstract: The CXC chemokine receptor 7 (CXCR7) has been reported to be involved in cell growth, metastasis and apoptosis in certain cancers. However, the function and molecular mechanisms of CXCR7 in human colorectal cancer (CRC) are still undefined. In the present study, sixty-eight cases of CRC tissues and corresponding adjacent non-cancer tissues (ANCT) were collected, and the expression of CXCR7 was assessed using immunohistochemistry (IHC) in biopsy samples. Furthermore, CXCR7 gene was silenced by small hairpin RNA-mediated lentiviral vector (Lv-shCXCR7), by transfection into human CRC cells (SW480 and HT-29). The levels of p-ERK, β-arrestin, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2) and caspase-3 (CAS-3) were detected by western blotting. Cell proliferative activities and invasive capability were respectively measured by MTT and Transwell assays. Cell apoptosis was analyzed by flow cytometry. The results demonstrated that CXCR7 expression was significantly upregulated in CRC tissues compared with the ANCT (54.4 vs. 36.8%, P=0.041), and correlated with Dukes staging and depth of invasion (P=0.007; P=0.002). Silencing of CXCR7 gene suppressed cell proliferation and invasion, and induced cell apoptosis in CRC cells with decreased expression of p-ERK, β-arrestin, PCNA and MMP-2 but increased expression of CAS-3. The tumor volumes in the SW480 subcutaneous tumor models treated with Lv-shCXCR7 were significantly smaller than those of the negative control (NC) and PBS groups (P<0.01). In conclusion, our findings indicate that upregulation of CXCR7 expression is associated with tumor invasion, and silencing of the CXCR7 gene represses the development of CRC cells through ERK and β-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of CRC.
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors: Xin-Xiang
authors: XX
authors: Li
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors: Hong-Tu
authors: HT
authors: Zheng
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors: Li-Yong
authors: LY
authors: Huang
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors: De-Bing
authors: DB
authors: Shi
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors: Jun-Jie
authors: JJ
authors: Peng
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors: Lei
authors: L
authors: Liang
authors: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors: San-Jun
authors: SJ
authors: Cai
mesh_terms: D000368:Aged; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D054387:Receptors, CXCR / Q000235:genetics* / Q000378:metabolism*; D000071557:beta-Arrestins
chemical_list: C501896:ACKR3 protein, human; D019390:Arrestins; C501897:Cmkor1 protein, mouse; D054387:Receptors, CXCR; D000071557:beta-Arrestins