一種經(jīng)過修改的信號(hào)傳導(dǎo)蛋白分子可能有能力阻斷導(dǎo)致黑素瘤細(xì)胞轉(zhuǎn)移的失誤。皮膚黑素瘤導(dǎo)致相對(duì)較少的癌癥,，但是它們的傳播傾向意味著這種疾病導(dǎo)致了皮膚癌死亡的大部分,。
Victoria Sherwood及其同事調(diào)查了阻斷Wnt5a分子的方法。這種分子的信號(hào)能增加細(xì)胞運(yùn)動(dòng)并導(dǎo)致黑素瘤的轉(zhuǎn)移,。這組作者最初嘗試通過上級(jí)調(diào)控者關(guān)閉Wnt5a的表達(dá),，結(jié)果被證明無(wú)效，這導(dǎo)致這組科學(xué)家把目標(biāo)直接對(duì)準(zhǔn)Wnt5a信號(hào)傳導(dǎo),。他們?nèi)缓箝_發(fā)出了一種稱為Box5的縮氨酸,，它可能有能力阻斷Wnt5的信號(hào)傳導(dǎo)活動(dòng)。在黑素瘤細(xì)胞系的測(cè)試中,，這種Box5分子通過抑制Wnt5a的鈣信號(hào)傳導(dǎo)（它對(duì)于細(xì)胞入侵至關(guān)重要）從而消除了這些細(xì)胞的遷移和入侵,。這組科學(xué)家說，Box5的這種直接效應(yīng)提示,，它可能對(duì)于開發(fā)針對(duì)轉(zhuǎn)移性黑素瘤和其他Wnt5a信號(hào)傳導(dǎo)迅速增殖的癌癥的療法有幫助,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS November 9, 2009, doi: 10.1073/pnas.0909409106
A t-butyloxycarbonyl-modified Wnt5a-derived hexapeptide functions as a potent antagonist of Wnt5a-dependent melanoma cell invasion
Veronika Jenei1,2, Victoria Sherwood1,3, Jillian Howlin, Rickard Linnskog, Annette S?fholm, Lena Axelsson and Tommy Andersson
Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Centre, Malm? University Hospital, SE-20502 Malm?, Sweden
The influential role of Wnt5a in tumor progression underscores the requirement for developing molecules that can target Wnt5a-mediated cellular responses. In the aggressive skin cancer, melanoma, elevated Wnt5a expression promotes cell motility and drives metastasis. Two approaches can be used to counteract these effects: inhibition of Wnt5a expression or direct blockade of Wnt5a signaling. We have investigated both options in the melanoma cell lines, A2058 and HTB63. Both express Frizzled-5, which has been implicated as the receptor for Wnt5a in melanoma cells. However, only the HTB63 cell line expresses and secretes Wnt5a. In these cells, the cytokine, TGFβ1, controlled the expression of Wnt5a, but due to the unpredictable effects of TGFβ1 signaling on melanoma cell motility, targeting Wnt5a signaling via TGFβ1 was an unsuitable strategy to pursue. We therefore attempted to target Wnt5a signaling directly. Exogenous Wnt5a stimulation of A2058 cells increased adhesion, migration and invasion, all crucial components of tumor metastasis, and the Wnt5a-derived N-butyloxycarbonyl hexapeptide (Met-Asp-Gly-Cys-Glu-Leu; 0.766 kDa) termed Box5, abolished these responses. Box5 also inhibited the basal migration and invasion of Wnt5a-expressing HTB63 melanoma cells. Box5 antagonized the effects of Wnt5a on melanoma cell migration and invasion by directly inhibiting Wnt5a-induced protein kinase C and Ca2+ signaling, the latter of which we directly demonstrate to be essential for cell invasion. The Box5 peptide directly inhibits Wnt5a signaling, representing an approach to anti-metastatic therapy for otherwise rapidly progressive melanoma, and for other Wnt5a-stimulated invasive cancers.
