文章基本信息

标题：Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells
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作者：Yang Li ; Shanshan Yang ; Nouara C. Sadaoui 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：7
页码：1-28
DOI：10.1016/j.isci.2020.101289
语种：English
出版社：Elsevier
摘要：SummaryChronic stress-related hormones modulate tumor pathogenesis at multiple levels; however, the molecular pathways involved in stress and cervical cancer progression are not well understood. We established a preclinical orthotopic mouse model of cervical cancer and used the model to show that daily restraint stress increased tumor growth and metastatic tumor burden. Exposure to norepinephrine significantly protected cervical cancer cells from anoikis. We demonstrated that YAP1 was dephosphorylated and translocated from the cytoplasm to the nucleus by norepinephrine, a process initiated by ADRB2/cAMP/protein kinase A activation. Furthermore, anoikis resistance and YAP1 activation induced by norepinephrine could be rescued by a broad β-adrenergic receptor antagonist, propranolol. Collectively, our results provide a pivotal molecular pathway for disrupting pro-tumor neuroendocrine signaling in cervical cancer.Highlights•Daily restraint stress increases tumor growth and metastatic tumor burden•Norepinephrine protects cervical cancer cells from anoikis•Norepinephrine induces YAP1 dephosphorylation and nuclear translocation•Norepinephrine - induced anoikis resistance can be reversed by propranololBiological Sciences; Cancer