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Title: MYBPH, a novel transcriptional target of NKX2-1/TTF-1, inhibits ROCK1 and actomyosin assembly, and reduces cell motility and tumor metastasis      
dateReleased:
12-22-2011
description:
Cell migration driven by actomyosin filament assembly is a critical step in tumour invasion and metastasis. Herein, we report identification of myosin binding protein H (MYBPH) as a transcriptional target of NKX2-1 (also known as TTF-1 and TITF1), a lineage-survival oncogene in lung adenocarcinoma. MYBPH inhibits assembly competence-conferring phosphorylation of the myosin regulatory light chain (RLC) as well as activating phosphorylation of LIM domain kinase (LIMK). These are unexpectedly implemented through direct physical interaction of MYBPH with Rho kinase 1 (ROCK1) rather than with RLC. In addition, MYBPH is shown to directly bind with non-muscle myosin heavy chain IIA (NMHC IIA), resulting in inhibition of NMHC IIA assembly. Thus, MYBPH plays multi-facetted roles in negative regulation of actomyosin organization, which in turn reduces cell motility, invasion, and metastasis. Finally, we also show that MYBPH is epigenetically inactivated by promoter DNA methylation in a fraction of lung adenocarcinomas abundantly expressing NKX2-1, which appears to be in accordance with its deleterious function for lung adenocarcinoma invasion and metastasis, as well as with the paradoxical association of NKX2-1 expression with favourable prognosis in lung adenocarcinoma patients. Dye-swap experiment, vector control vs. transiently transfectanted with TTF-1 in HPL1D, immortalized human peripheral lung epithelial cell line.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-26721
refinement:
raw
alternateIdentifiers:
26721
keywords:
functional genomics
dateModified:
05-04-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AGIL-28
name:
Agilent Whole Human Genome Microarray 4x44K 014850 G4112F (85 cols x 532 rows)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-26721/E-GEOD-26721.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-26721/E-GEOD-26721.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26721
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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