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LKB1 Controls Human Bronchial Epithelial Morphogenesis Through P114RhoGEF-dependent RhoA Activation

Overview
Journal Mol Cell Biol
Specialty Cell Biology
Date 2013 May 8
PMID 23648482
Citations 31
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Abstract

LKB1 is a Ser/Thr kinase that plays an important role in controlling both energy metabolism and cell polarity in metazoan organisms. LKB1 is also a tumor suppressor, and homozygous, inactivating mutations are found in a wide range of human cancers. In lung cancer, inactivating mutations are found in 10 to 50% of cases, but the consequences of functional loss in this context are poorly understood. We report here that LKB1 is required for the maturation of apical junctions in the human bronchial epithelial cell line 16HBE14o- (16HBE). This activity is dependent on an interaction with the Rho guanine nucleotide exchange factor p114RhoGEF but is independent of LKB1 kinase activity. Together, LKB1 and p114RhoGEF control RhoA activity in these cells to promote apical junction assembly.

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References
1.
Sanchez-Cespedes M . A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene. 2007; 26(57):7825-32. DOI: 10.1038/sj.onc.1210594. View

2.
Martin S, St Johnston D . A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity. Nature. 2003; 421(6921):379-84. DOI: 10.1038/nature01296. View

3.
Gloerich M, Ten Klooster J, Vliem M, Koorman T, Zwartkruis F, Clevers H . Rap2A links intestinal cell polarity to brush border formation. Nat Cell Biol. 2012; 14(8):793-801. DOI: 10.1038/ncb2537. View

4.
Roy B, Kohno T, Iwakawa R, Moriguchi T, Kiyono T, Morishita K . Involvement of LKB1 in epithelial-mesenchymal transition (EMT) of human lung cancer cells. Lung Cancer. 2010; 70(2):136-45. DOI: 10.1016/j.lungcan.2010.02.004. View

5.
Zhang L, Li J, Young L, Caplan M . AMP-activated protein kinase regulates the assembly of epithelial tight junctions. Proc Natl Acad Sci U S A. 2006; 103(46):17272-7. PMC: 1859922. DOI: 10.1073/pnas.0608531103. View