Wnt信号通路
黑色素瘤
癌症研究
生物
上皮-间质转换
PTEN公司
细胞生长
转移
基因敲除
信号转导
癌症
细胞培养
细胞生物学
PI3K/AKT/mTOR通路
遗传学
作者
Bo Dong,Laura Simonson,Samantha Vold,Ethan Oldham,Lillian Barten,Nihal Ahmad,Haiyan Chang
标识
DOI:10.1016/j.jid.2022.09.658
摘要
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 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. Spatial Cancer Systems Biology Resolves Heterotypic Interactions and Identifies Disruption of Spatial Hierarchy as a Pathological Driver EventJournal of Investigative DermatologyVol. 143Issue 8PreviewSpatially annotated single-cell datasets provide unprecedented opportunities to dissect cell-cell communication in development and disease. Heterotypic signaling includes interactions between different cell types and is well established in tissue development and spatial organization. Epithelial organization requires several different programs that are tightly regulated. Planar cell polarity is the organization of epithelial cells along the planar axis, orthogonal to the apical-basal axis. Here, we investigate planar cell polarity factors and explore the implications of developmental regulators as malignant drivers. Full-Text PDF
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