{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:04:19Z","timestamp":1788026659590,"version":"build-2784847793"},"reference-count":82,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010751","name":"ANID, FONDECYT","doi-asserted-by":"publisher","award":["11181105"],"award-info":[{"award-number":["11181105"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010751","name":"ANID, FONDECYT","doi-asserted-by":"publisher","award":["11191195"],"award-info":[{"award-number":["11191195"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010751","name":"ANID, FONDECYT","doi-asserted-by":"publisher","award":["1201217"],"award-info":[{"award-number":["1201217"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The oxidized low-density lipoprotein receptor 1 (LOX-1) is one of the most important receptors for modified LDLs, such as oxidated (oxLDL) and acetylated (acLDL) low-density lipoprotein. LOX-1 and oxLDL are fundamental in atherosclerosis, where oxLDL\/LOX1 promotes ROS generation and NF-\u03baB activation inducing the expression of IL-6, a STAT3 activator. Furthermore, LOX-1\/oxLDL function has been associated with other diseases, such as obesity, hypertension, and cancer. In prostate cancer (CaP), LOX-1 overexpression is associated with advanced stages, and its activation by oxLDL induces an epithelial-mesenchymal transition, increasing angiogenesis and proliferation. Interestingly, enzalutamide-resistant CaP cells increase the uptake of acLDL. Enzalutamide is an androgen receptor (AR) antagonist for castration-resistant prostate cancer (CRPC) treatment, and a high percentage of patients develop a resistance to this drug. The decreased cytotoxicity is promoted in part by STAT3 and NF-\u03baB activation that induces the secretion of the pro-inflammatory program and the expression of AR and its splicing variant AR-V7. Here, we demonstrate for the first time that oxLDL\/LOX-1 increases ROS levels and activates NF-\u03baB, inducing IL-6 secretion and the activation of STAT3 in CRPC cells. Furthermore, oxLDL\/LOX1 increases AR and AR-V7 expression and decreases enzalutamide cytotoxicity in CRPC. Thus, our investigation suggests that new factors associated with cardiovascular pathologies, such as LOX-1\/oxLDL, may also promote important signaling axes for the progression of CRPC and its resistance to drugs used for its treatment.<\/jats:p>","DOI":"10.3390\/ijms24065082","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T03:11:39Z","timestamp":1678158699000},"page":"5082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-\u03baB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects"],"prefix":"10.3390","volume":"24","author":[{"given":"Felix","family":"Duprat","sequence":"first","affiliation":[{"name":"Laboratory of Lipoproteins and Cancer, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Robles","sequence":"additional","affiliation":[{"name":"Laboratory of Lipoproteins and Cancer, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Paz","family":"Castillo","sequence":"additional","affiliation":[{"name":"Laboratory of Lipoproteins and Cancer, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerko","family":"Rivas","sequence":"additional","affiliation":[{"name":"Laboratory of Lipoproteins and Cancer, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Mondaca","sequence":"additional","affiliation":[{"name":"Laboratory of Lipoproteins and Cancer, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nery","family":"Jara","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Roa","sequence":"additional","affiliation":[{"name":"Laboratory of Lipoproteins and Cancer, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0929-133X","authenticated-orcid":false,"given":"Romina","family":"Bertinat","sequence":"additional","affiliation":[{"name":"Centro de Microscop\u00eda Avanzada, CMA-BIO BIO, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Toledo","sequence":"additional","affiliation":[{"name":"Biotechnology and Biopharmaceuticals Laboratory, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4668-4984","authenticated-orcid":false,"given":"Cristian","family":"Paz","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0544-4463","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Gonz\u00e1lez-Chavarr\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Lipoproteins and Cancer, Pathophysiology Department, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.metabol.2012.07.024","article-title":"Lipoprotein(a) metabolism: Potential sites for therapeutic targets","volume":"62","author":"Huang","year":"2013","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1097\/00041433-199412000-00002","article-title":"Characterization of low-density lipoprotein subclasses: Methodologic approaches and clinical relevance","volume":"5","author":"Austin","year":"1994","journal-title":"Curr. 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