title: Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis.
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 FAKY397, 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 pFAKY397, 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.
authors.affiliation: Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. asood@mdanderson.org
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Guillermo N
authors.initials: GN
authors.lastname: Armaiz-Pena
authors.forename: Jyotsnabaran
authors.initials: J
authors.lastname: Halder
authors.forename: Alpa M
authors.initials: AM
authors.lastname: Nick
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stone
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Amy R
authors.initials: AR
authors.lastname: Carroll
authors.forename: Whitney A
authors.initials: WA
authors.lastname: Spannuth
authors.forename: Michael T
authors.initials: MT
authors.lastname: Deavers
authors.forename: Julie K
authors.initials: JK
authors.lastname: Allen
authors.forename: Liz Y
authors.initials: LY
authors.lastname: Han
authors.forename: Aparna A
authors.initials: AA
authors.lastname: Kamat
authors.forename: Mian M K
authors.initials: MM
authors.lastname: Shahzad
authors.forename: Bradley W
authors.initials: BW
authors.lastname: McIntyre
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Diaz-Montero
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Jennings
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Lin
authors.forename: William M
authors.initials: WM
authors.lastname: Merritt
authors.forename: Koen
authors.initials: K
authors.lastname: DeGeest
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Vivas-Mejia
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schaller
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lutgendorf
mesh_terms: D000199:Actins / Q000378:metabolism; D018663:Adrenergic Agents / Q000378:metabolism*; D000818:Animals; D023102:Anoikis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009638:Norepinephrine / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D000199:Actins; D018663:Adrenergic Agents; D051416:Focal Adhesion Protein-Tyrosine Kinases; D009638:Norepinephrine; D004837:Epinephrine
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