Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.
Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.
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frizzled-7 表达的下调会降低结肠癌细胞的存活、侵袭和转移能力。
DOI：
10.1038/sj.bjc.6605307
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发表时间：
2009-10-20
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
经典Wnt信号通路在大多数散发性结直肠癌（CRC）中被激活。我们先前报道了FZD 7在结肠癌细胞中作为经典Wnt信号通路的受体发挥作用。在这项研究中，我们研究了FZD 7在结肠癌细胞的存活，侵袭和转移能力中的功能。FZD 7_siRNA转染降低HT-29和HCT-116结肠癌细胞的细胞活力。FZD7_siRNA转染HCT-116细胞后，c-Jun的表达、JNK和c-Jun的磷酸化以及RhoA的活化均受到抑制。FZD 7_siRNA转染的HCT-116细胞体外侵袭活性和Wnt靶基因表达也降低。与对照相比，稳定的FZD7_siRNA HCT-116细胞转染子在scid小鼠中的肝转移降低至40-50%。采用实时荧光定量PCR检测135例大肠癌组织中FZD 7的mRNA水平。FZD 7 mRNA水平在II、III或IV期肿瘤中显著高于非肿瘤组织（P<0.005），并且在具有较高FZD 7表达的那些患者中总生存期较短（P<0.001）。这些数据表明，FZD 7可能通过非经典Wnt信号传导途径以及经典途径参与结肠癌细胞的存活、侵袭和转移能力的增强。
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.
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影响因子：
8
作者：
Belguise, K;Kersual, N;Chalbos, D
通讯作者：
Chalbos, D
影响因子：
3.7
作者：
Railo, Antti;Nagy, Irina I.;Vainio, Seppo
通讯作者：
Vainio, Seppo
DOI：
10.1073/pnas.96.4.1603
发表时间：
1999-02-16
影响因子：
11.1
作者：
Mann, B;Gelos, M;Hanski, C
通讯作者：
Hanski, C
影响因子：
11.2
作者：
Hiendlmeyer, E;Regus, S;Jung, A
通讯作者：
Jung, A
影响因子：
11.2
作者：
Croft, DR;Sahai, E;Olson, MF
通讯作者：
Olson, MF