{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:03:50Z","timestamp":1785409430753,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010041","name":"Tianjin Municipal Science and Technology Commission","doi-asserted-by":"crossref","award":["24JCZDJC00120"],"award-info":[{"award-number":["24JCZDJC00120"]}],"id":[{"id":"10.13039\/501100010041","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010041","name":"Tianjin Municipal Science and Technology Commission","doi-asserted-by":"crossref","award":["24PTLYHZ00280"],"award-info":[{"award-number":["24PTLYHZ00280"]}],"id":[{"id":"10.13039\/501100010041","id-type":"DOI","asserted-by":"crossref"}]},{"award":["24JCZDJC00120"],"award-info":[{"award-number":["24JCZDJC00120"]}],"id":[{"id":"https:\/\/ror.org\/03wb1xh22","id-type":"ROR","asserted-by":"publisher"}]},{"award":["24PTLYHZ00280"],"award-info":[{"award-number":["24PTLYHZ00280"]}],"id":[{"id":"https:\/\/ror.org\/03wb1xh22","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor prognosis. While sorafenib serves as the first-line therapy for advanced HCC, its efficacy is frequently hampered by side effects and the development of drug resistance, necessitating the development of novel agents to enhance HCC sensitivity to sorafenib. In this study, we demonstrate that the antihistamine astemizole significantly enhanced the antitumor efficacy of sorafenib in HCC cell lines. This combination treatment cooperatively inhibited HCC cells\u2019 proliferation and induced cell cycle arrest at the G1 phase, as evidenced by decreased cyclin D1 and p-Rb levels and increased p27 expression. Furthermore, the combination of astemizole and sorafenib synergistically inhibited HCC cells\u2019 migration, invasion, and adhesion. It also reduced F-actin polymerization and the expression of metastasis-regulating proteins, including p-Integrin\u03b21, FAK, and MMP1. Additionally, the combination treatment suppressed tube formation in HUVECs, accompanied by downregulation of HIF-1\u03b1 and reduced VEGF secretion. Co-inhibition of Eag1 and the ERK\/MAPK signaling pathway may underlie the enhanced anti-HCC effects of sorafenib by astemizole. Collectively, these findings indicate that astemizole significantly enhanced the antitumor activity of sorafenib by inhibiting proliferation, metastasis, and angiogenesis in HCC cells, suggesting its potential as a promising adjuvant to improve sorafenib-based therapy in HCC.<\/jats:p>","DOI":"10.3390\/cimb48050451","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:09:33Z","timestamp":1777388973000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Antihistamine Astemizole Potentiates the Antitumor Efficacy of Sorafenib in Hepatocellular Carcinoma by Suppressing Proliferation, Metastasis, and Angiogenesis"],"prefix":"10.3390","volume":"48","author":[{"given":"Yixuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"},{"name":"International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"},{"name":"Key Laboratory of Immune Microenvironment and Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"},{"name":"International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"},{"name":"Key Laboratory of Immune Microenvironment and Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuting","family":"Yang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"},{"name":"International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"},{"name":"Key Laboratory of Immune Microenvironment and Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"},{"name":"International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"},{"name":"Key Laboratory of Immune Microenvironment and Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"},{"name":"International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"},{"name":"Key Laboratory of Immune Microenvironment and Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8064-1435","authenticated-orcid":false,"given":"Dexin","family":"Kong","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"},{"name":"International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"},{"name":"Key Laboratory of Immune Microenvironment and Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"},{"name":"International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"},{"name":"Key Laboratory of Immune Microenvironment and Diseases (Ministry of Education), Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular carcinoma","volume":"400","author":"Vogel","year":"2022","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"188314","DOI":"10.1016\/j.bbcan.2019.188314","article-title":"Challenges in liver cancer and possible treatment approaches","volume":"1873","author":"Anwanwan","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA) Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1111\/apt.70576","article-title":"Editorial: Tumour Burden Score and Extrahepatic Progression After TACE\u2014Refining Risk Stratification Beyond the Liver","volume":"63","author":"Su","year":"2026","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"973","DOI":"10.4254\/wjh.v9.i22.973","article-title":"Extrahepatic metastasis of hepatocellular carcinoma to the paravertebral muscle: A case report","volume":"9","author":"Takahashi","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma: Trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S228","DOI":"10.3350\/cmh.2024.0824","article-title":"Hepatocellular carcinoma: Updates on epidemiology, surveillance, diagnosis and treatment","volume":"31","author":"Hwang","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/cac2.12414","article-title":"Cancer-associated fibroblast-derived secreted phosphoprotein 1 contributes to resistance of hepatocellular carcinoma to sorafenib and lenvatinib","volume":"43","author":"Eun","year":"2023","journal-title":"Cancer Commun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Philippi, Z., Reddy, K.D., Malik, S., Al-Khalil, Z., and Dbouk, N. (2025). Systemic Therapy for Unresectable Hepatocellular Carcinoma: Current Landscape and Future Directions. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26135994"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41392-020-0187-x","article-title":"The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects","volume":"5","author":"Tang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2174\/187152011795347513","article-title":"Astemizole: An Old Anti-histamine as a New Promising Anti-cancer Drug","volume":"11","author":"Camacho","year":"2011","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Canella, R., Brugnoli, F., Gallo, M., Keillor, J.W., Terrazzan, A., Ferrari, E., Grassilli, S., Gates, E.W.J., Volinia, S., and Bertagnolo, V. (2022). A Multidisciplinary Approach Establishes a Link between Transglutaminase 2 and the Kv10.1 Voltage-Dependent K+ Channel in Breast Cancer. Cancers, 15.","DOI":"10.3390\/cancers15010178"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1083\/jcb.201404136","article-title":"Targeting potassium channels in cancer","volume":"206","author":"Huang","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/med.21808","article-title":"Overcoming challenges of HERG potassium channel liability through rational design: Eag1 inhibitors for cancer treatment","volume":"42","author":"Toplak","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhou, S., Song, X., Zeng, W., and Chen, D. (2025). Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation. Pharmaceuticals, 18.","DOI":"10.3390\/ph18101521"},{"key":"ref_16","first-page":"139","article-title":"Eag1 channels as potential early-stage biomarkers of hepatocellular carcinoma","volume":"10","author":"Escobar","year":"2016","journal-title":"Biologics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"432","DOI":"10.31083\/ph.2012.1742","article-title":"Blood-brain barrier models as tools in drug discovery: Assessment of the transport ranking of antihistaminic drugs","volume":"67","author":"Neuhaus","year":"2012","journal-title":"Pharmazie"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3892\/ol.2025.15272","article-title":"The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review)","volume":"30","author":"Wei","year":"2025","journal-title":"Oncol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Quiroz, J., Garc\u00eda-Becerra, R., Santos-Mart\u00ednez, N., Barrera, D., Ordaz-Rosado, D., Avila, E., Halhali, A., Villanueva, O., Ibarra-S\u00e1nchez, M.J., and Esparza-L\u00f3pez, J. (2014). In vivo dual targeting of the oncogenic Ether-\u00e0-go-go-1 potassium channel by calcitriol and astemizole results in enhanced antineoplastic effects in breast tumors. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-745"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5795","DOI":"10.2147\/OTT.S144506","article-title":"The combination astemizole\u2013gefitinib as a potential therapy for human lung cancer","volume":"10","author":"Vera","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s41419-021-03805-6","article-title":"BKM120 sensitizes glioblastoma to the PARP inhibitor rucaparib by suppressing homologous recombination repair","volume":"12","author":"Zhang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116796","DOI":"10.1016\/j.bcp.2025.116796","article-title":"Glutamine transporter inhibitor enhances the sensitivity of NSCLC to trametinib through GSDME-dependent pyroptosis","volume":"233","author":"Liu","year":"2025","journal-title":"Biochem. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13577","DOI":"10.3390\/ijms140713577","article-title":"In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells","volume":"14","author":"Zhao","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzym. Regul."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/jpy.13250","article-title":"Flow cytometry and 5-ethynyl-2\u2019-deoxyuridine (EdU) labeling to detect the cell cycle dynamics of Phaeodactylum tricornutum under light","volume":"58","author":"Zhang","year":"2022","journal-title":"J. Phycol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6149","DOI":"10.1007\/s13277-015-3299-0","article-title":"Astemizole-based anticancer therapy for hepatocellular carcinoma (HCC), and Eag1 channels as potential early-stage markers of HCC","volume":"36","author":"Herrera","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41392-023-01705-z","article-title":"Targeting the RAS\/RAF\/MAPK pathway for cancer therapy: From mechanism to clinical studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41568-020-00329-7","article-title":"The matrix in cancer","volume":"21","author":"Cox","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.tcb.2012.07.001","article-title":"Actin cortex mechanics and cellular morphogenesis","volume":"22","author":"Salbreux","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41573-021-00284-4","article-title":"Emerging therapeutic opportunities for integrin inhibitors","volume":"21","author":"Slack","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nrc3792","article-title":"FAK in cancer: Mechanistic findings and clinical applications","volume":"14","author":"Sulzmaier","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cell.2010.03.015","article-title":"Matrix Metalloproteinases: Regulators of the Tumor Microenvironment","volume":"141","author":"Kessenbrock","year":"2010","journal-title":"Cell"},{"key":"ref_33","first-page":"193","article-title":"Angiogenic signaling pathways and anti-angiogenic therapy for cancer","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","article-title":"Activation of Vascular Endothelial Growth Factor Gene Transcription by Hypoxia-Inducible Factor 1","volume":"16","author":"Forsythe","year":"2023","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.3748\/wjg.v29.i17.2571","article-title":"Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma","volume":"29","author":"Camacho","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.bbamcr.2011.01.025","article-title":"Regulation of IGF-1-dependent cyclin D1 and E expression by hEag1 channels in MCF-7 cells: The critical role of hEag1 channels in G1 phase progression","volume":"1813","author":"Borowiec","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e4544","DOI":"10.15252\/embr.201745440","article-title":"Perturbing mitosis for anti-cancer therapy: Is cell death the only answer?","volume":"19","author":"Haschka","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Liu, Y., Park, S., and Li, Y. (2025). Breaking Cancer\u2019s Momentum: CDK4\/6 Inhibitors and the Promise of Combination Therapy. Cancers, 17.","DOI":"10.3390\/cancers17121941"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1158\/1541-7786.MCR-17-0602","article-title":"Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation Induces a Potent and Durable Response in Breast Cancer Cells","volume":"16","author":"Patel","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ouadid-Ahidouch, H., and Ahidouch, A. (2013). K+ channels and cell cycle progression in tumor cells. Front. Physiol., 4.","DOI":"10.3389\/fphys.2013.00220"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Dryer, S.E., Lin, H., Li, Z., Chen, C., Luo, X., Xiao, J., Dong, D., Lu, Y., Yang, B., and Wang, Z. (2011). Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether \u00c0 Go-Go K+ Channel. PLoS ONE, 6, Erratum in: PLoS ONE\u00a02011, 30, 524-532.","DOI":"10.1371\/annotation\/45b3e6bc-1065-4357-b215-465176dcc269"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.canlet.2019.07.007","article-title":"Higd-1a regulates the proliferation of pancreatic cancer cells through a pERK\/p27KIP1\/pRB pathway","volume":"461","author":"An","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/path.5246","article-title":"RN181 is a tumour suppressor in gastric cancer by regulation of the ERK\/MAPK\u2013cyclin D1\/CDK4 pathway","volume":"248","author":"Wang","year":"2019","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.apsb.2015.07.005","article-title":"Cancer metastases: Challenges and opportunities","volume":"5","author":"Guan","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41568-018-0038-z","article-title":"Every step of the way: Integrins in cancer progression and metastasis","volume":"18","author":"Hamidi","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11033-023-08920-5","article-title":"Adhesion, metastasis, and inhibition of cancer cells: A comprehensive review","volume":"51","author":"Yayan","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1126\/science.aay7794","article-title":"Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration","volume":"368","author":"Bisaria","year":"2020","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10456-022-09849-2","article-title":"The rising impact of angiogenesis research","volume":"25","author":"Griffioen","year":"2022","journal-title":"Angiogenesis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in Signaling and Disease: Beyond Discovery and Development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"145796","DOI":"10.1016\/j.gene.2021.145796","article-title":"Up-down regulation of HIF-1\u03b1 in cancer progression","volume":"798","author":"Rashid","year":"2021","journal-title":"Gene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00232-016-9944-8","article-title":"Eag1 Voltage-Dependent Potassium Channels: Structure, Electrophysiological Characteristics, and Function in Cancer","volume":"250","author":"Wang","year":"2017","journal-title":"J. Membr. Biol."},{"key":"ref_52","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/s12935-025-04020-5","article-title":"The Kv10.1 potassium channel, driver of hypoxia-induced EMT and breast cancer cell aggressiveness","volume":"25","author":"Gutierrez","year":"2025","journal-title":"Cancer Cell Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109892","DOI":"10.1016\/j.biopha.2020.109892","article-title":"Macrophage migration inhibitory factor regulates integrin-\u03b21 and cyclin D1 expression via ERK pathway in podocytes","volume":"124","author":"Chen","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1476-4598-9-17","article-title":"CXCR4\/SDF1 mediate hypoxia induced chondrosarcoma cell invasion through ERK signaling and increased MMP1 expression","volume":"9","author":"Sun","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41419-018-1010-2","article-title":"CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met\/ERK\/Elk-1\/HIF-1\u03b1\/VEGF-A pathway in colorectal cancer","volume":"9","author":"Xu","year":"2018","journal-title":"Cell Death Dis."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/5\/451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:17:45Z","timestamp":1777436265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/5\/451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,26]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cimb48050451"],"URL":"https:\/\/doi.org\/10.3390\/cimb48050451","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,26]]}}}