ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
The β2-adrenoceptor activates a positive cAMP-calcium feedforward loop to drive breast cancer cell invasion.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- Cardio-Oncology: A Myriad of Relationships Between Cardiovascular Disease and Cancer.Frontiers in cardiovascular medicine · 2022Pooled it
- Post-Diagnostic Beta Blocker Use and Prognosis of Ovarian Cancer: A Systematic Review and Meta-Analysis of 11 Cohort Studies With 20,274 Patients.Frontiers in oncology · 2021Pooled it
- Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.Oncotarget · 2017Pooled it
- Review
- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- Synergistic combination of the adrenergic antagonist SR59230A with common chemotherapeutic drugs and target therapies in cancer and endothelial cells.Investigational new drugs · 2025Article
- Tumor-Associated Sympathetic Nerves Promote the Progression of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis.iScience · 2025Article
- Review
- Sympathetic nerve signals: orchestrators of mammary development and stem cell vitality.Journal of molecular cell biology · 2024Article
- Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy.Biological procedures online · 2024Review
- Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.International journal of molecular sciences · 2024Article
- Psychosocial stressors and breast cancer gene expression in the Black Women's Health Study.Breast cancer research and treatment · 2024Article
- βCells · 2024Article
- Inside the Biology of the β3-Adrenoceptor.Biomolecules · 2024Review
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Chronic stress induces pulmonary epithelial cells to produce acetylcholine that remodels lung pre-metastatic niche of breast cancer by enhancing NETosis.Journal of experimental & clinical cancer research : CR · 2023Article
- The neural addiction of cancer.Nature reviews. Cancer · 2023Review
- The Secretome of Parental and Bone Metastatic Breast Cancer Elicits Distinct Effects in Human Osteoclast Activity after Activation of β2 Adrenergic Signaling.Biomolecules · 2023Article
- ß-Adrenoreceptors in Human Cancers.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of the sympathetic nervous system by stress increases breast cancer metastasis in vivo. Preclinical studies suggest that stress activates β-adrenoceptors (βARs) to enhance metastasis from primary tumors and that β-blockers may be protective in breast cancer. However, the subtype of βAR that mediates this effect, as well as the signaling mechanisms underlying increased tumor cell dissemination, remain unclear. We show that the β2AR is the only functionally relevant βAR subtype in the highly metastatic human breast cancer cell line MDA-MB-231HM. β2AR activation results in elevated cAMP (formoterol pEC50 9.86 ± 0.32), increased intracellular Ca(2+) (formoterol pEC50 8.20 ± 0.33) and reduced phosphorylated ERK (pERK; formoterol pIC50 11.62 ± 0.31). We demonstrate that a highly amplified positive feedforward loop between the cAMP and Ca(2+) pathways is responsible for efficient inhibition of basal pERK. Importantly, activation of the β2AR increased invasion (formoterol area under the curve [AUC] relative to vehicle: 1.82 ± 0.36), which was dependent on the cAMP/Ca(2+) loop (formoterol AUC in the presence of 2'5'-dideoxyadenosine 0.64 ± 0.03, or BAPTA-AM 0.45 ± 0.23) but independent of inhibition of basal pERK1/2 (vehicle AUC with U0126 0.60 ± 0.30). Specifically targeting the positive feedforward cAMP/Ca(2+) loop may be beneficial for the development of therapeutics to slow disease progression in patients with breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.