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

Antonis Kourtidis, Siu P. Ngok, Pamela Pulimeno, Ryan W. Feathers, Lomeli R. Carpio, Tiany R. Baker, Jennifer M. Carr, Irene K. Yan, Sahra Borges, Edith A. Perez, Peter Storz, John A III Copland, Tushar C Patel, E Aubrey Thompson, Sandra Citi, Panagiotis Z Anastasiadis

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53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1145-1157
Number of pages13
JournalNature
Volume17
Issue number9
DOIs
StatePublished - Sep 1 2015

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Kourtidis, A., Ngok, S. P., Pulimeno, P., Feathers, R. W., Carpio, L. R., Baker, T. R., Carr, J. M., Yan, I. K., Borges, S., Perez, E. A., Storz, P., Copland, J. A. III., Patel, T. C., Thompson, E. A., Citi, S., & Anastasiadis, P. Z. (2015). Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity. Nature, 17(9), 1145-1157. https://doi.org/10.1038/ncb3227