SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1.
The human airway is lined with respiratory epithelial cells, which create a critical barrier through the formation of apical tight junctions. To investigate the molecular mechanisms underlying this process, an RNAi screen for guanine nucleotide exchange factors (GEFs) was performed in human bronchial epithelial cells (16HBE). We report that SOS1, acting through the Ras/MEK/ERK pathway, is essential for tight junction formation. Global microarray analysis identifies epithelial membrane protein 1 (EMP1), an integral tetraspan membrane protein, as a major transcriptional target. EMP1 is indispensable for tight junction formation and function in 16HBE cells and in a human airway basal progenitor-like cell line (BCi-NS1.1). Furthermore, EMP1 is significantly downregulated in human lung cancers. Together, these data identify important roles for SOS1/Ras and EMP1 in tight junction assembly during airway morphogenesis.
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Joanne
J
Durgan
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Guangbo
G
Tao
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA.
Matthew S
MS
Walters
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Oliver
O
Florey
MRC Laboratory for Molecular Cell Biology, University College London, London, UK.
Anja
A
Schmidt
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA.
Vanessa
V
Arbelaez
Molecular Pharmacology & Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Neal
N
Rosen
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA.
Ronald G
RG
Crystal
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA halla@mskcc.org.
Alan
A
Hall
D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020837:SOS1 Protein / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D020837:SOS1 Protein; C097051:epithelial membrane protein-1; D018631:ras Proteins
EMP1; Ras; SOS1; lung; tight junctions