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Original citation: J Clin Invest. 2013;123(5):2119-2130. https://doi.org/10.1172/JCI65425. Citation for this corrigendum: J Clin Invest. 2021;131(7):e149893. https://doi.org/10.1172/JCI149893. The Editors previously posted an Expression of Concern for this article regarding images in [...]

Author(s): Premal H. Thaker [sup.1], Liz Y. Han [sup.1], Aparna A. Kamat [sup.1], Jesusa M. Arevalo [sup.2], Rie Takahashi [sup.2], Chunhua Lu [sup.1], Nicholas B. Jennings [sup.1], Guillermo Armaiz-Pena [sup.1], [...]

Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum [...]

Introduction There is growing evidence supporting the role of stress biology in cardiovascular (1), cancer (2), (3), and other disease states. Several epidemiological and experimental studies have suggested that behavioral [...], 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.sup.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.sup.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.

Author(s): Premal H Thaker [1, 10]; Liz Y Han [1, 10]; Aparna A Kamat [1, 10]; Jesusa M Arevalo [2]; Rie Takahashi [2]; Chunhua Lu [1]; Nicholas B Jennings [1]; [...]