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

Yang Li; Shanshan Yang; Nouara C Sadaoui; Wei Hu; Santosh K Dasari; Lingegowda S Mangala; Yunjie Sun; Shuangtao Zhao; Linghua Wang; Yuan Liu; Lois M Ramondetta; Ke Li; Chong Lu; Yu Kang; Steve W Cole; Susan K Lutgendorf; Anil K Sood

doi:10.1016/j.isci.2020.101289

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

iScience. 2020 Jul 24;23(7):101289. doi: 10.1016/j.isci.2020.101289. Epub 2020 Jun 20.

Authors

Yang Li¹, Shanshan Yang², Nouara C Sadaoui³, Wei Hu³, Santosh K Dasari³, Lingegowda S Mangala³, Yunjie Sun³, Shuangtao Zhao⁴, Linghua Wang⁴, Yuan Liu³, Lois M Ramondetta³, Ke Li⁵, Chong Lu⁵, Yu Kang⁵, Steve W Cole⁶, Susan K Lutgendorf⁷, Anil K Sood⁸

Affiliations

¹ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Department of Gynecologic Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, China.
³ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, China.
⁶ 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.
⁷ Department of Psychological & Brain Sciences, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Department of Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
⁸ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: [email protected].

Abstract

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.

Keywords: Biological Sciences; Cancer.

Abstract

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