title: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity.
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.
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Antonis
authors: A
authors: Kourtidis
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Siu P
authors: SP
authors: Ngok
authors: Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, CH-1211, Geneva 4, Switzerland.
authors: Pamela
authors: P
authors: Pulimeno
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Ryan W
authors: RW
authors: Feathers
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Lomeli R
authors: LR
authors: Carpio
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Tiffany R
authors: TR
authors: Baker
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Jennifer M
authors: JM
authors: Carr
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Irene K
authors: IK
authors: Yan
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Sahra
authors: S
authors: Borges
authors: Division of Hematology/Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Edith A
authors: EA
authors: Perez
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Peter
authors: P
authors: Storz
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: John A
authors: JA
authors: Copland
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Tushar
authors: T
authors: Patel
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: E Aubrey
authors: EA
authors: Thompson
authors: Department of Cell Biology and Institute of Genetics and Genomics of Geneva, University of Geneva, 30 quai Ernest-Ansermet, CH-1211, Geneva 4, Switzerland.
authors: Sandra
authors: S
authors: Citi
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Panos Z
authors: PZ
authors: Anastasiadis
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D018938:Caco-2 Cells; D015820:Cadherins / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D051177:Catenins; C474043:DGCR8 protein, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C533786:PLEKHA7 protein, human; D016601:RNA-Binding Proteins; D019061:src-Family Kinases; C517918:DROSHA protein, human; D043244:Ribonuclease III; D000095002:Delta Catenin