Journal article
Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis
The Journal of clinical investigation, Vol.120(5), pp.1515-1523
05/03/2010
DOI: 10.1172/JCI40802
PMCID: PMC2860925
PMID: 20389021
Abstract
Chronic stress is associated with hormonal changes that are known to affect multiple systems, including the immune and endocrine systems, but the effects of stress on cancer growth and progression are not fully understood. Here, we demonstrate that human ovarian cancer cells exposed to either norepinephrine or epinephrine exhibit lower levels of anoikis, the process by which cells enter apoptosis when separated from ECM and neighboring cells. In an orthotopic mouse model of human ovarian cancer, restraint stress and the associated increases in norepinephrine and epinephrine protected the tumor cells from anoikis and promoted their growth by activating focal adhesion kinase (FAK). These effects involved phosphorylation of FAK
Y397
, which was itself associated with actin-dependent Src interaction with membrane-associated FAK. Importantly, in human ovarian cancer patients, behavioral states related to greater adrenergic activity were associated with higher levels of pFAK
Y397
, which was in turn linked to substantially accelerated mortality. These data suggest that FAK modulation by stress hormones, especially norepinephrine and epinephrine, can contribute to tumor progression in patients with ovarian cancer and may point to potential new therapeutic targets for cancer management.
Details
- Title: Subtitle
- Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis
- Creators
- Anil K Sood - Department of Gynecologic OncologyGuillermo N Armaiz-Pena - Department of Gynecologic OncologyJyotsnabaran Halder - Department of Gynecologic OncologyAlpa M Nick - Department of Gynecologic OncologyRebecca L Stone - Department of Gynecologic OncologyWei Hu - Department of Gynecologic OncologyAmy R Carroll - Department of Gynecologic OncologyWhitney A Spannuth - Department of Gynecologic OncologyMichael T Deavers - Department of Gynecologic OncologyJulie K Allen - Department of Gynecologic OncologyLiz Y Han - Department of Gynecologic OncologyAparna A Kamat - Department of Gynecologic OncologyMian M.K Shahzad - Department of Gynecologic OncologyBradley W McIntyre - Department of Gynecologic OncologyClaudia M Diaz-Montero - Department of Gynecologic OncologyNicholas B Jennings - Department of Gynecologic OncologyYvonne G Lin - Department of Gynecologic OncologyWilliam M Merritt - Department of Gynecologic OncologyKoen DeGeest - Department of Gynecologic OncologyPablo E Vivas-Mejia - Department of Gynecologic OncologyGabriel Lopez-Berestein - Department of Gynecologic OncologyMichael D Schaller - Department of Gynecologic OncologySteven W Cole - Department of Gynecologic OncologySusan K Lutgendorf - Department of Gynecologic Oncology
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.120(5), pp.1515-1523
- DOI
- 10.1172/JCI40802
- PMID
- 20389021
- PMCID
- PMC2860925
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Language
- English
- Date published
- 05/03/2010
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984065884502771
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