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题目:: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity.
作者:: Kourtidis(Antonis),Ngok(Siu P),Pulimeno(Pamela),Feathers(Ryan W),Carpio(Lomeli R),Baker(Tiffany R),Carr(Jennifer M),Yan(Irene K),Borges(Sahra),Perez(Edith A),Storz(Peter),Copland(John A),Patel(Tushar),Thompson(E Aubrey),Citi(Sandra),Anastasiadis(Panos Z)
状态:: 发布时间2015-08-28 , 更新时间 2016-10-19
期刊:: Nat Cell Biol
摘要:: E-cadherin and p120 catenin (p120) are essential for epithelial homeostasis, but can also exert pro-tumorigenic activities. Here, we resolve this apparent paradox by identifying two spatially and functionally distinct junctional complexes in non-transformed polarized epithelial cells: one growth suppressing at the apical zonula adherens (ZA), defined by the p120 partner PLEKHA7 and a non-nuclear subset of the core microprocessor components DROSHA and DGCR8, and one growth promoting at basolateral areas of cell-cell contact containing tyrosine-phosphorylated p120 and active Src. Recruitment of DROSHA and DGCR8 to the ZA is PLEKHA7 dependent. The PLEKHA7-microprocessor complex co-precipitates with primary microRNAs (pri-miRNAs) and possesses pri-miRNA processing activity. PLEKHA7 regulates the levels of select miRNAs, in particular processing of miR-30b, to suppress expression of cell transforming markers promoted by the basolateral complex, including SNAI1, MYC and CCND1. Our work identifies a mechanism through which adhesion complexes regulate cellular behaviour and reveals their surprising association with the microprocessor.
语言:: eng
DOI:

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