Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity

Nat Cell Biol. 2015 Sep;17(9):1145-57. doi: 10.1038/ncb3227. Epub 2015 Aug 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / metabolism
  • Animals
  • Antigens, CD
  • Caco-2 Cells
  • Cadherins / physiology*
  • Carrier Proteins / metabolism
  • Catenins / metabolism*
  • Dogs
  • Humans
  • Madin Darby Canine Kidney Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Transport
  • RNA Interference
  • RNA Processing, Post-Transcriptional
  • RNA-Binding Proteins / metabolism
  • Ribonuclease III / metabolism
  • src-Family Kinases / metabolism*

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Carrier Proteins
  • Catenins
  • DGCR8 protein, human
  • MIRN30 microRNA, human
  • MicroRNAs
  • PLEKHA7 protein, human
  • RNA-Binding Proteins
  • delta catenin
  • src-Family Kinases
  • DROSHA protein, human
  • Ribonuclease III