Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature cell biology, 2015-09, Vol.17 (9), p.1145

Ort / Verlag

England

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.