{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:16Z","timestamp":1787028436568,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research &amp; Developmental Support Agency  APVV","award":["APVV-16-0343"],"award-info":[{"award-number":["APVV-16-0343"]}]},{"name":"Slovak Scientific Grant Agency VEGA","award":["VEGA 2\/090\/20, VEGA 2\/0064\/18"],"award-info":[{"award-number":["VEGA 2\/090\/20, VEGA 2\/0064\/18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The coexistence of cancer and other concomitant diseases is very frequent and has substantial implications for treatment decisions and outcomes. Beta-blockers, agents that block the beta-adrenergic receptors, have been related also to cancers. In the model of multicellular spheroids formed by colorectal cancer cells we described a crosstalk between beta-blockade by propranolol and tumour microenvironment. Non-selective beta-blocker propranolol decreased ability of tumour cells to adapt to hypoxia by reducing levels of HIF1\u03b1 and carbonic anhydrase IX in 3D spheroids. We indicated a double action of propranolol in the tumour microenvironment by inhibiting the stability of HIF1\u03b1, thus mediating decrease of CA IX expression and, at the same time, by its possible effect on CA IX activity by decreasing the activity of protein kinase A (PKA). Moreover, the inhibition of \u03b2-adrenoreceptors by propranolol enhanced apoptosis, decreased number of mitochondria and lowered the amount of proteins involved in oxidative phosphorylation (V-ATP5A, IV-COX2, III-UQCRC2, II-SDHB, I-NDUFB8). Propranolol reduced metastatic potential, viability and proliferation of colorectal cancer cells cultivated in multicellular spheroids. To choose the right treatment strategy, it is extremely important to know how the treatment of concomitant diseases affects the superior microenvironment that is directly related to the efficiency of anti-cancer therapy<\/jats:p>","DOI":"10.3390\/ijms21228760","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T10:46:26Z","timestamp":1605782786000},"page":"8760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol\u2014Impact on Progression and Metastatic Potential of Colorectal Cancer Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Monika","family":"Barathova","sequence":"first","affiliation":[{"name":"Biomedical Research Centre, Department of Tumor Biology, Institute of Virology, Slovak Academy of Sciences Dubravska cesta 9, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Grossmannova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Department of Tumor Biology, Institute of Virology, Slovak Academy of Sciences Dubravska cesta 9, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Belvoncikova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Department of Tumor Biology, Institute of Virology, Slovak Academy of Sciences Dubravska cesta 9, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Kubasova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Department of Tumor Biology, Institute of Virology, Slovak Academy of Sciences Dubravska cesta 9, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Simko","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Department of Tumor Biology, Institute of Virology, Slovak Academy of Sciences Dubravska cesta 9, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Skubla","sequence":"additional","affiliation":[{"name":"Ruzinov Hospital, University Hospital Bratislava, Ruzinovska 6, 82101 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Csaderova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Department of Tumor Biology, Institute of Virology, Slovak Academy of Sciences Dubravska cesta 9, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaromir","family":"Pastorek","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Department of Tumor Biology, Institute of Virology, Slovak Academy of Sciences Dubravska cesta 9, 84505 Bratislava, Slovakia"},{"name":"Faculty of Medicine, Slovak Medical University, Limbov\u00e1 12, 83303 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dronkers, E.A., Mes, S.W., Wieringa, M.H., van der Schroeff, M.P., and Baatenburg de Jong, R.J. (2015). Noncompliance to guidelines in head and neck cancer treatment; associated factors for both patient and physician. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1523-3"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.radonc.2013.07.005","article-title":"Impact of comorbidity on treatment outcome in head and neck squamous cell carcinoma\u2014A systematic review","volume":"110","author":"Boje","year":"2014","journal-title":"Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8580","DOI":"10.1038\/s41598-019-44969-8","article-title":"The effects of comorbidity on colorectal cancer mortality in an Australian cancer population","volume":"9","author":"Pule","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3322\/caac.21342","article-title":"The impact of comorbidity on cancer and its treatment","volume":"66","author":"Sarfati","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1200\/CCI.19.00107","article-title":"Treatment Patterns for Chronic Comorbid Conditions in Patients With Cancer Using a Large-Scale Observational Data Network","volume":"4","author":"Chen","year":"2020","journal-title":"JCO Clin. Cancer Inform."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jaccao.2019.11.009","article-title":"Hypertension in Cancer Patients and Survivors: Epidemiology, Diagnosis, and Management","volume":"1","author":"Cohen","year":"2019","journal-title":"JACC CardioOncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/cncr.28509","article-title":"Annual Report to the Nation on the status of cancer, 1975\u20132010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer","volume":"120","author":"Edwards","year":"2014","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.annonc.2019.10.023","article-title":"Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations","volume":"31","author":"Curigliano","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s13054-015-0913-x","article-title":"Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults","volume":"19","author":"Ali","year":"2015","journal-title":"Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/01.wad.0000155067.16313.5e","article-title":"Propranolol for disruptive behaviors in nursing home residents with probable or possible Alzheimer disease: A placebo-controlled study","volume":"19","author":"Peskind","year":"2005","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1097\/00005053-198605000-00005","article-title":"Propranolol treatment of assaultive patients with organic brain disease. A double-blind crossover, placebo-controlled study","volume":"174","author":"Greendyke","year":"1986","journal-title":"J. Nerv. Ment. Dis."},{"key":"ref_12","first-page":"779","article-title":"Treatment with beta-blockers and reduced disease progression in patients with thick melanoma","volume":"171","author":"Grazzini","year":"2011","journal-title":"Arch. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1200\/JCO.2010.33.4441","article-title":"Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer","volume":"29","author":"Lei","year":"2011","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ygyno.2012.07.102","article-title":"Impact of beta blockers on epithelial ovarian cancer survival","volume":"127","author":"Diaz","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/cncr.28546","article-title":"Stage-specific associations between beta blocker use and prognosis after colorectal cancer","volume":"120","author":"Jansen","year":"2014","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jhep.2016.04.019","article-title":"ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1alpha","volume":"65","author":"Wu","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nrc1820","article-title":"The influence of bio-behavioural factors on tumour biology: Pathways and mechanisms","volume":"6","author":"Antoni","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/ncponc1134","article-title":"Do stress-related psychosocial factors contribute to cancer incidence and survival?","volume":"5","author":"Chida","year":"2008","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.eururo.2013.01.007","article-title":"Association between use of beta-blockers and prostate cancer-specific survival: A cohort study of 3561 prostate cancer patients with high-risk or metastatic disease","volume":"65","author":"Grytli","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10552-015-0693-2","article-title":"Prostate cancer risk among users of digoxin and other antiarrhythmic drugs in the Finnish Prostate Cancer Screening Trial","volume":"27","author":"Kaapu","year":"2016","journal-title":"Cancer Causes Control"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kulik, G. (2019). ADRB2-Targeting Therapies for Prostate Cancer. Cancers, 11.","DOI":"10.3390\/cancers11030358"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s10549-013-2654-3","article-title":"Therapeutic effect of beta-blockers in triple-negative breast cancer postmenopausal women","volume":"140","author":"Botteri","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"628","DOI":"10.18632\/oncotarget.197","article-title":"Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival","volume":"1","author":"Powe","year":"2010","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.3892\/or.2016.4710","article-title":"Inhibition of beta2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative beta-blockade","volume":"35","author":"Choy","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6446","DOI":"10.18632\/oncotarget.14119","article-title":"Use of non-selective beta-blockers is associated with decreased tumor proliferative indices in early stage breast cancer","volume":"8","author":"Montoya","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1158\/1055-9965.EPI-11-0249","article-title":"beta-Blockers and survival among Danish patients with malignant melanoma: A population-based cohort study","volume":"20","author":"Lemeshow","year":"2011","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s00432-014-1658-7","article-title":"Meta-analysis of the effects of beta blocker on survival time in cancer patients","volume":"140","author":"Choi","year":"2014","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1093\/ije\/dyt196","article-title":"Beta-blocker usage and breast cancer survival: A nested case-control study within a UK clinical practice research datalink cohort","volume":"42","author":"Cardwell","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1016\/j.ejca.2013.07.141","article-title":"beta-Blocker use and all-cause mortality of melanoma patients: Results from a population-based Dutch cohort study","volume":"49","author":"Livingstone","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/bjd.12894","article-title":"Beta-blocker usage after malignant melanoma diagnosis and survival: A population-based nested case-control study","volume":"170","author":"McCourt","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"36.e1","DOI":"10.1016\/j.urolonc.2016.08.013","article-title":"Evaluation of beta-blockers and survival among hypertensive patients with renal cell carcinoma","volume":"35","author":"Parker","year":"2017","journal-title":"Urol. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bja.2018.03.024","article-title":"Effect of beta-blockers on cancer recurrence and survival: A meta-analysis of epidemiological and perioperative studies","volume":"121","author":"Yap","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"ref_33","first-page":"295","article-title":"Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium","volume":"35","author":"Bristow","year":"1989","journal-title":"Mol. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1158\/1078-0432.CCR-11-0641","article-title":"Molecular pathways: Beta-adrenergic signaling in cancer","volume":"18","author":"Cole","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_35","first-page":"2877","article-title":"Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment","volume":"9","author":"Pastorek","year":"1994","journal-title":"Oncogene"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.semcancer.2014.08.002","article-title":"Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use","volume":"31","author":"Pastorek","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_37","first-page":"7075","article-title":"Hypoxia-inducible expression of tumor-associated carbonic anhydrases","volume":"60","author":"Wykoff","year":"2000","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1158\/0008-5472.CAN-11-2520","article-title":"Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors","volume":"71","author":"Ditte","year":"2011","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1016\/j.ejca.2005.09.011","article-title":"The role of carbonic anhydrase IX overexpression in kidney cancer","volume":"41","author":"Dorai","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.2174\/138161210793429832","article-title":"Carbonic anhydrase IX as an anticancer therapy target: Preclinical evaluation of internalizing monoclonal antibody directed to catalytic domain","volume":"16","author":"Zatovicova","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11371","DOI":"10.1038\/ncomms11371","article-title":"Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells","volume":"7","author":"Menard","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/sj.bjc.6602861","article-title":"Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a metalloprotease-dependent process regulated by TACE\/ADAM17","volume":"93","author":"Zatovicova","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Vidlickova, I., Dequiedt, F., Jelenska, L., Sedlakova, O., Pastorek, M., Stuchlik, S., Pastorek, J., Zatovicova, M., and Pastorekova, S. (2016). Apoptosis-induced ectodomain shedding of hypoxia-regulated carbonic anhydrase IX from tumor cells: A double-edged response to chemotherapy. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2267-4"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1053\/gast.1997.v112.pm9024293","article-title":"Carbonic anhydrase IX, MN\/CA IX: Analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts","volume":"112","author":"Pastorekova","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_45","first-page":"680","article-title":"Repurposing Drugs in Oncology (ReDO)-Propranolol as an anti-cancer agent","volume":"10","author":"Pantziarka","year":"2016","journal-title":"Ecancermedicalscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/SLA.0b013e318254ce7a","article-title":"Propranolol induces regression of hemangioma cells through HIF-1alpha-mediated inhibition of VEGF-A","volume":"256","author":"Chim","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e90240","DOI":"10.1172\/jci.insight.90240","article-title":"Hypoxia sensing through beta-adrenergic receptors","volume":"1","author":"Cheong","year":"2016","journal-title":"JCI Insight"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7050","DOI":"10.1038\/s41598-018-25340-9","article-title":"Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression","volume":"8","author":"Brohee","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41389-018-0090-2","article-title":"beta2-Adrenergic receptor modulates mitochondrial metabolism and disease progression in recurrent\/metastatic HPV(+) HNSCC","volume":"7","author":"Lucido","year":"2018","journal-title":"Oncogenesis"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lucido, C.T., Miskimins, W.K., and Vermeer, P.D. (2018). Propranolol Promotes Glucose Dependence and Synergizes with Dichloroacetate for Anti-Cancer Activity in HNSCC. Cancers, 10.","DOI":"10.3390\/cancers10120476"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"161","DOI":"10.18632\/oncotarget.1083","article-title":"Anti-tumor activity of the beta-adrenergic receptor antagonist propranolol in neuroblastoma","volume":"5","author":"Wolter","year":"2014","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/0042-6822(92)90464-Z","article-title":"A novel quasi-viral agent, MaTu, is a two-component system","volume":"187","author":"Pastorekova","year":"1992","journal-title":"Virology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nprot.2008.226","article-title":"Spheroid-based drug screen: Considerations and practical approach","volume":"4","author":"Friedrich","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0959-8049(99)00221-X","article-title":"Comorbidity and colorectal cancer according to subsite and stage: A population-based study","volume":"36","author":"Coebergh","year":"2000","journal-title":"Eur. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e1097","DOI":"10.1097\/MD.0000000000001097","article-title":"Propranolol Reduces Cancer Risk: A Population-Based Cohort Study","volume":"94","author":"Chang","year":"2015","journal-title":"Medicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"221","DOI":"10.15698\/cst2019.07.192","article-title":"Stress and catecholamines modulate the bone marrow microenvironment to promote tumorigenesis","volume":"3","author":"Hanns","year":"2019","journal-title":"Cell Stress"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1039\/C4TX00160E","article-title":"Functional xenobiotic metabolism and efflux transporters in trout hepatocyte spheroid cultures","volume":"4","author":"Uchea","year":"2015","journal-title":"Toxicol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jconrel.2012.04.045","article-title":"Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy","volume":"164","author":"Mehta","year":"2012","journal-title":"J. Control Rel."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10121","DOI":"10.1038\/s41598-017-09549-8","article-title":"Hypoxia induces cancer-associated cAMP\/PKA signalling through HIF-mediated transcriptional control of adenylyl cyclases VI and VII","volume":"7","author":"Simko","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1074\/jbc.M110978200","article-title":"Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect","volume":"277","author":"Minchenko","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10863-007-9081-2","article-title":"HIF-1 mediates the Warburg effect in clear cell renal carcinoma","volume":"39","author":"Semenza","year":"2007","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10892","DOI":"10.1074\/jbc.M800102200","article-title":"Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13023-015-0343-5","article-title":"Propranolol reduces viability and induces apoptosis in hemangioblastoma cells from von Hippel-Lindau patients","volume":"10","author":"Albinana","year":"2015","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.3892\/or.2015.3874","article-title":"Antiproliferative effects of beta-blockers on human colorectal cancer cells","volume":"33","author":"Coelho","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/jcp.25092","article-title":"Selective beta2-AR Blockage Suppresses Colorectal Cancer Growth Through Regulation of EGFR-Akt\/ERK1\/2 Signaling, G1-Phase Arrest, and Apoptosis","volume":"231","author":"Chin","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_66","first-page":"334","article-title":"Propranolol as a novel adjunctive treatment for head and neck squamous cell carcinoma","volume":"41","author":"Wolter","year":"2012","journal-title":"J. Otolaryngol. Head Neck Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4161\/cbt.10.1.11944","article-title":"beta2-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NFkappaB and AP-1","volume":"10","author":"Zhang","year":"2010","journal-title":"Cancer Biol. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1002\/ijc.21723","article-title":"The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB\/c nude mice is inhibited by beta-blockers","volume":"118","author":"Palm","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/onc.2015.58","article-title":"beta2-AR signaling controls trastuzumab resistance-dependent pathway","volume":"35","author":"Liu","year":"2016","journal-title":"Oncogene"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.mrrev.2012.08.001","article-title":"In vitro cell migration and invasion assays","volume":"752","author":"Kramer","year":"2013","journal-title":"Mutat. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3892\/ijo.2015.3038","article-title":"The stress hormone norepinephrine increases migration of prostate cancer cells in vitro and in vivo","volume":"47","author":"Barbieri","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_72","first-page":"1471","article-title":"beta-arrestin2 mediates beta-2 adrenergic receptor signaling inducing prostate cancer cell progression","volume":"26","author":"Zhang","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Huang, Z., Li, G., Zhang, Z., Gu, R., Wang, W., Lai, X., Cui, Z.K., Zeng, F., Xu, S., and Deng, F. (2019). beta2AR-HIF-1alpha-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6301-1"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/s41419-019-2030-2","article-title":"Chronic stress promotes gastric cancer progression and metastasis: An essential role for ADRB2","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1074\/jbc.M111.286062","article-title":"Carbonic anhydrase IX interacts with bicarbonate transporters in lamellipodia and increases cell migration via its catalytic domain","volume":"287","author":"Svastova","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"420747","DOI":"10.1155\/2008\/420747","article-title":"Genevestigator v3: A reference expression database for the meta-analysis of transcriptomes","volume":"2008","author":"Hruz","year":"2008","journal-title":"Adv. Bioinform."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. 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