Department of Dermatology, The School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA; Program in Genetics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Dermatology, The School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J Invest Dermatol. 2023 Apr;143(4):621-629.e6. doi: 10.1016/j.jid.2022.09.658. Epub 2022 Nov 9.
FZD6 is a key gene that controls tissue polarity during development. Increasing evidence suggests that it also plays active roles in various cancers. In this study, we show that FZD6 is overexpressed in multiple melanoma cell lines and human samples. Knockdown or knockout of FZD6 does not affect cell proliferation but significantly reduces the invasive ability of melanoma cells. In addition, we have found that knockout of Fzd6 dramatically reduces lung metastasis in the Pten/BRaf mouse model of melanoma. Mechanistic studies in vitro and in vivo reveal a surprising involvement of canonical Wnt signaling and epithelial‒mesenchymal pathway in the FZD6-mediated invasive phenotype. Together, our study supports a promoter role of FZD6 in melanoma progression.
FZD6 是一个在发育过程中控制组织极性的关键基因。越来越多的证据表明，它在各种癌症中也发挥着积极的作用。在这项研究中，我们表明 FZD6 在多种黑色素瘤细胞系和人类样本中过表达。FZD6 的敲低或敲除并不影响细胞增殖，但显著降低了黑色素瘤细胞的侵袭能力。此外，我们发现 Fzd6 的敲除显著减少了黑色素瘤 Pten/BRaf 小鼠模型中的肺转移。体外和体内的机制研究揭示了经典 Wnt 信号通路和上皮-间充质途径在 FZD6 介导的侵袭表型中的惊人参与。总之，我们的研究支持 FZD6 在黑色素瘤进展中的启动子作用。
