Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220304764 |
| _version_ | 1818149619428753408 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yang Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T13:09:55Z |
| format | Article |
| id | doaj.art-aafb654e476b47ddb4c1d3c01818360f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-11T13:09:55Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-aafb654e476b47ddb4c1d3c01818360f2022-12-22T01:06:13ZengElsevieriScience2589-00422020-07-01237101289Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer CellsYang Li0Shanshan Yang1Nouara C. Sadaoui2Wei Hu3Santosh K. Dasari4Lingegowda S. Mangala5Yunjie Sun6Shuangtao Zhao7Linghua Wang8Yuan Liu9Lois M. Ramondetta10Ke Li11Chong Lu12Yu Kang13Steve W. Cole14Susan K. Lutgendorf15Anil K. Sood16Department 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, ChinaDepartment of Gynecologic Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaCousins 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, USADepartment 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, USADepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004220304764Biological SciencesCancer |
| spellingShingle | 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 Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells iScience Biological Sciences Cancer |
| title | Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells |
| title_full | Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells |
| title_fullStr | Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells |
| title_full_unstemmed | Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells |
| title_short | Sustained Adrenergic Activation of YAP1 Induces Anoikis Resistance in Cervical Cancer Cells |
| title_sort | sustained adrenergic activation of yap1 induces anoikis resistance in cervical cancer cells |
| topic | Biological Sciences Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220304764 |
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