Ueno K, Hazama S, Mitomori S, Nishioka M, Suehiro Y, Hirata H, Oka M, Imai K, Dahiya R, Hinoda Y
Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Br J Cancer. 2009 Oct 20;101(8):1374-81. doi: 10.1038/sj.bjc.6605307. Epub 2009 Sep 22.
The canonical Wnt signalling pathway is activated in most sporadic colorectal cancers (CRCs). We previously reported that FZD7 functions as a receptor for the canonical Wnt signalling pathway in colon cancer cells.
In this study, we examined the function of FZD7 in survival, invasion and metastatic capabilities of colon cancer cells. FZD7_siRNA transfection decreased cell viability of HT-29 and HCT-116 colon cancer cells. Expression of c-Jun, phosphorylation of JNK and c-Jun, and activation of RhoA were suppressed after FZD7_siRNA transfection into HCT-116 cells. In vitro invasion activity and Wnt target gene expression were also reduced in HCT-116 cells transfected with FZD7_siRNA. Liver metastasis of stable FZD7_siRNA HCT-116 cell transfectants in scid mice was decreased to 40-50% compared to controls. The mRNA levels of FZD7 in 135 primary CRC tissues were examined by real-time PCR. FZD7 mRNA levels were significantly higher in stage II, III or IV tumours than in non-tumour tissues (P<0.005), and overall survival was shorter in those patients with higher FZD7 expression (P<0.001).
These data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway.
在大多数散发性结直肠癌（CRC）中，经典Wnt信号通路被激活。我们之前报道过，FZD7在结肠癌细胞中作为经典Wnt信号通路的受体发挥作用。
在本研究中，我们检测了FZD7在结肠癌细胞存活、侵袭和转移能力方面的作用。FZD7_siRNA转染降低了HT - 29和HCT - 116结肠癌细胞的活力。将FZD7_siRNA转染到HCT - 116细胞后，c - Jun的表达、JNK和c - Jun的磷酸化以及RhoA的激活均受到抑制。用FZD7_siRNA转染的HCT - 116细胞的体外侵袭活性和Wnt靶基因表达也降低。与对照组相比，scid小鼠中稳定转染FZD7_siRNA的HCT - 116细胞的肝转移率降低至40 - 50%。通过实时PCR检测了135例原发性CRC组织中FZD7的mRNA水平。FZD7 mRNA水平在II期、III期或IV期肿瘤中显著高于非肿瘤组织（P<0.005），且FZD7表达较高的患者总生存期较短（P<0.001）。
这些数据表明，FZD7可能通过非经典Wnt信号通路以及经典通路参与增强结肠癌细胞的存活、侵袭和转移能力。
