Distinct E-cadherin-based Complexes Regulate Cell Behaviour Through MiRNA Processing or Src and P120 catenin Activity

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2015 Aug 25

PMID 26302406

Citations 59

Authors

Antonis Kourtidis

Siu P Ngok

Pamela Pulimeno

Ryan W Feathers

Lomeli R Carpio

Tiffany R Baker

Jennifer M Carr

Irene K Yan

Sahra Borges

Edith A Perez

Peter Storz

John A Copland

Tushar Patel

E Aubrey Thompson

Sandra Citi

Panos Z Anastasiadis

Affiliations

Soon will be listed here.

Abstract

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.

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