Document Detail

Isoform-specific modulation of pressure-stimulated cancer cell proliferation and adhesion by α-actinin.
MedLine Citation:
PMID:  21906716     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Intratumoral pressure may stimulate cancer proliferation whereas intravascular pressure promotes metastatic adhesion. α-Actinin proteins facilitate focal adhesion formation and link focal adhesion complexes to the cytoskeleton. We hypothesized that α-actinin is the mechanotransducer that mediates the effects of pressure on cancer cell proliferation and adhesion.
METHODS: We treated SW620 colon cancer cells with specific short interfering RNA to reduce α-actinin-1 and/or α-actinin-4, the 2 key epithelial isoforms. Proliferation was measured in adherent cells by microculture tetrazolium (MTT) assay after 24 hours at ambient or 40 mm Hg increased pressure. For comparison, we evaluated the effects of 30 minutes of ambient or 15-mm Hg increased pressure on adhesion of suspended SW620 cells. Because the transcription factor nuclear factor-κB (NF-κB) influences proliferation, we used co-immunoprecipitation to evaluate NF-κB-α-actinin association and a lentiviral reporter assay for NF-κB activity.
RESULTS: A total of 40 mm Hg increased pressure increased SW620 proliferation 41% ± 6% (n = 10; P < .05) versus ambient pressure controls. Reducing α-actinin-1 and α-actinin-4 together or α-actinin-4 alone blocked this effect, but reducing α-actinin-1 alone did not (n = 6; P < .05). We observed a 72% ± 11% increase in NF-κB activity (n = 6; P < .05), and increased association between NF-κB and α-actinin-4 in adherent cells under pressure. NF-κB and α-actinin-1 did not co-immunoprecipitate. However, reducing α-actinin-4 did not prevent pressure-induced NF-κB activation (n = 8).
CONCLUSIONS: α-actinin-4 may mediate pressure stimulation of proliferation within large rapidly growing tumors, perhaps by binding transcription factors such as NF-κB. α-actinins may be important targets to inhibit cancer proliferation and metastasis.
Christina Downey; David H Craig; Marc D Basson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-09-09
Journal Detail:
Title:  American journal of surgery     Volume:  202     ISSN:  1879-1883     ISO Abbreviation:  Am. J. Surg.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-21     Completed Date:  2011-12-29     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  0370473     Medline TA:  Am J Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  520-3     Citation Subset:  AIM; IM    
Copyright Information:
Published by Elsevier Inc.
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MeSH Terms
Actinin / metabolism*
Cell Adhesion / physiology*
Cell Line, Tumor
Cell Proliferation*
Colonic Neoplasms / metabolism*
Mechanotransduction, Cellular / physiology
NF-kappa B / biosynthesis
RNA, Small Interfering
Grant Support
Reg. No./Substance:
0/NF-kappa B; 0/RNA, Small Interfering; 11003-00-2/Actinin

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