Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells

iScience

Shanshan Yang¹  Susan K. Lutgendorf²  Linghua Wang³  Yuan Liu³  Lois M. Ramondetta⁴  Wei Hu⁴  Ke Li⁴  Yunjie Sun⁴  Yang Li⁴  Lingegowda S. Mangala⁴  Santosh K. Dasari⁴  Shuangtao Zhao⁴  Nouara C. Sadaoui⁵  Yu Kang⁶  Steve W. Cole⁶  Chong Lu⁶  Anil K. Sood⁷ 

[1] Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China;Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA;Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Department of Gynecologic Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, China;Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, China;;Department of Psychological &

关键词: Biological Sciences;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Chronic 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.

【 授权许可】

Unknown