PMID- 32234582 OWN - NLM STAT- MEDLINE DCOM- 20200804 LR - 20211104 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 113 DP - 2020 May TI - The stress hormone norepinephrine promotes tumor progression through beta2-adrenoreceptors in oral cancer. PG - 104712 LID - S0003-9969(20)30090-X [pii] LID - 10.1016/j.archoralbio.2020.104712 [doi] AB - OBJECTIVE: Chronic stress hormone norepinephrine (NE) has been previously reported to play a role in the development of cancer, but the correlation between NE and oral squamous cell carcinoma (OSCC) progression is not well understood. METHOD: To address this, the expression of adrenergic receptors (ARs) in human OSCC cell lines and clinic OSCC samples was detected, and the role of NEin vivo and in vitro was further investigated. RESULTS: It was found that beta2-AR was the main AR of NE in OSCC. Stimulation of OSCC cells with NE significantly increased the OSCC proliferation and invasion, which was, however, blocked by beta2-AR inhibitor. NE could induce the phosphorylation of extracellular regulated protein kinases (ERK) and cAMP-response element binding protein (CREB). Inhibition of ERK and CREB pathway abrogated NE-induced OSCC invasion and proliferation. NE could enhance cancer stem cells (CSCs)-like phenotype and up-regulate the expression of stemness marker. In tumor-bearing nude mice, it was found that consecutive administration of NE significantly promoted the tumor growth, while daily injection of beta2-AR inhibitor blocked this phenomenon. CONCLUSIONS: Those findings indicated a critical role of the chronic stress hormone NE in OSCC progression. Inhibition of beta2-AR may serve as a potential therapeutic strategy for protecting OSCC patients from chronic stress related deleterious effect. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Zhang, Bowen AU - Zhang B AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Wu, Chenzhou AU - Wu C AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Chen, Wen AU - Chen W AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Qiu, Ling AU - Qiu L AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Li, Shensui AU - Li S AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Wang, Tao AU - Wang T AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Xie, Huixu AU - Xie H AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Li, Yi AU - Li Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Li, Chunjie AU - Li C AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Li, Longjiang AU - Li L AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: muzili63@163.com. LA - eng PT - Journal Article DEP - 20200321 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 RN - 0 (Adrenergic beta-2 Receptor Antagonists) RN - 0 (CREB1 protein, human) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Receptors, Adrenergic, beta-2) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - X4W3ENH1CV (Norepinephrine) SB - IM EIN - Arch Oral Biol. 2022 Jan;133:105295. PMID: 34735928 MH - Adrenergic beta-2 Receptor Antagonists MH - Animals MH - Carcinoma, Squamous Cell/*pathology MH - Cell Line, Tumor MH - Cyclic AMP Response Element-Binding Protein MH - Extracellular Signal-Regulated MAP Kinases MH - Humans MH - Mice MH - Mice, Nude MH - Mouth Neoplasms/*pathology MH - Norepinephrine/*metabolism MH - Receptors, Adrenergic, beta-2/*metabolism MH - Signal Transduction OTO - NOTNLM OT - Cancer stem cells OT - Norepinephrine OT - Oral squamous cell carcinoma OT - Stress OT - beta-adrenergic receptors COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2020/04/03 06:00 MHDA- 2020/08/05 06:00 CRDT- 2020/04/03 06:00 PHST- 2019/10/02 00:00 [received] PHST- 2020/03/06 00:00 [revised] PHST- 2020/03/15 00:00 [accepted] PHST- 2020/04/03 06:00 [pubmed] PHST- 2020/08/05 06:00 [medline] PHST- 2020/04/03 06:00 [entrez] AID - S0003-9969(20)30090-X [pii] AID - 10.1016/j.archoralbio.2020.104712 [doi] PST - ppublish SO - Arch Oral Biol. 2020 May;113:104712. doi: 10.1016/j.archoralbio.2020.104712. Epub 2020 Mar 21.