表型
TCF4型
小眼畸形相关转录因子
Wnt信号通路
生物
表型转换
连环素
黑色素瘤
细胞生物学
细胞
基因表达
癌症研究
基因
信号转导
转录因子
遗传学
增强子
作者
Ossia M. Eichhoff,Ashani T. Weeraratna,Marie Zipser,Laurence Denat,Daniel Widmer,Mai Xu,Lydia Kriegl,Thomas Kirchner,Lionel Larue,Reinhard Dummer,Keith S. Hoek
标识
DOI:10.1111/j.1755-148x.2011.00871.x
摘要
Summary Recent observations suggest that melanoma cells drive disease progression by switching back and forth between phenotypic states of proliferation and invasion. Phenotype switching has been linked to changes in Wnt signalling, and we therefore looked for cell phenotype‐specific differences in the levels and activity of β‐catenin and its LEF/TCF co‐factors. We found that while cytosolic β‐catenin distribution is phenotype‐specific (membrane‐associated in proliferative cells and cytosolic in invasive cells), its nuclear distribution and activity is not. Instead, the expression patterns of two β‐catenin co‐factors, LEF1 and TCF4, are both phenotype‐specific and inversely correlated. LEF1 is preferentially expressed by differentiated/proliferative phenotype cells and TCF4 by dedifferentiated/invasive phenotype cells. Knock‐down experiments confirmed that these co‐factors are important for the phenotype‐specific expression of M‐MITF, WNT5A and other genes and that LEF1 suppresses TCF4 expression independently of β‐catenin. Our data show that melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity.
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