{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T05:20:33Z","timestamp":1787462433752,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["NexGenerationEU-PNRR-MAD-2022-12375679"],"award-info":[{"award-number":["NexGenerationEU-PNRR-MAD-2022-12375679"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["NexGenerationEU-PNRR-MAD-2022-12375679"],"award-info":[{"award-number":["NexGenerationEU-PNRR-MAD-2022-12375679"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. Smoking is the primary etiological factor, but growing evidence suggests the involvement of estrogen in its development and progression, although its role remains unclear. This study explores: (i) the effects induced by estrogen, namely, 17\u03b2-estradiol (E2), alone or in combination with a mixture of inflammatory cytokines (Mix), in two human NSCLC cell lines, A549 and Calu1, and (ii) whether and how tumor cells can modulate the activation of normal lung fibroblasts. We found that E2 significantly enhances migration, invasion, and epithelial\u2013mesenchymal transition in NSCLC cells, as well as their resistance to cisplatin, particularly in combination with Mix. Pharmacological inhibition of ER\u03b2 reversed the E2-induced effects, implicating ER\u03b2 in E2-mediated signaling. Furthermore, E2 increased autophagic flux and induced a shift toward secretory autophagy and the release of extracellular vesicles, which activated normal lung fibroblasts, as demonstrated by the increased expression of \u03b1-SMA, FAP, PDGFR-\u03b2, and PDPN. The clinical relevance of these data was supported by computational analyses revealing an elevated expression of the Mix gene signature, including TGF-\u03b2, IL-6, IL-8, CCXL-16, and ER\u03b2, which was associated with shorter overall survival in NSCLC patients. This molecular profile was linked to the elevated expression of secretory autophagy genes and cancer-associated fibroblast markers. Validation in three large clinical cohorts (TCGA-LUNG, OAK and POPLAR) strengthens the clinical relevance of this E2-related pro-tumor axis while suggesting a promising therapeutic avenue for NSCLC patients.<\/jats:p>","DOI":"10.3390\/ijms27167490","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:37:34Z","timestamp":1787312254000},"page":"7490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["17\u03b2-Estradiol Modulates Cancer Cell\u2013Fibroblast Communication via Autophagy-Mediated Extracellular Vesicle Secretion and Promotes Poor Prognosis in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4501-8661","authenticated-orcid":false,"given":"Rosa","family":"Vona","sequence":"first","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0 [Italian National Institute of Health], Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Cittadini","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Ascione","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0 [Italian National Institute of Health], Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-5958","authenticated-orcid":false,"given":"Lucrezia","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0 [Italian National Institute of Health], Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Fecchi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-2376","authenticated-orcid":false,"given":"Lucia","family":"Bertuccini","sequence":"additional","affiliation":[{"name":"Core Facilities, Italian National Institute of Health, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-4679","authenticated-orcid":false,"given":"Annalisa","family":"Tocci","sequence":"additional","affiliation":[{"name":"Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53-00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9656-7436","authenticated-orcid":false,"given":"Lorenzo","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53-00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4628-0696","authenticated-orcid":false,"given":"Federica","family":"Felicetti","sequence":"additional","affiliation":[{"name":"Core Facilities, Italian National Institute of Health, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ortona","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0 [Italian National Institute of Health], Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Nistic\u00f2","sequence":"additional","affiliation":[{"name":"Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53-00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1970-3297","authenticated-orcid":false,"given":"Anna Maria","family":"Mileo","sequence":"additional","affiliation":[{"name":"Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53-00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-3752","authenticated-orcid":false,"given":"Paola","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0 [Italian National Institute of Health], Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00026.2006","article-title":"Estrogen receptors: How do they signal and what are their targets","volume":"87","author":"Heldring","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.steroids.2006.11.019","article-title":"Estrogen receptor signaling pathways in human non-small cell lung cancer","volume":"72","author":"Chen","year":"2007","journal-title":"Steroids"},{"key":"ref_3","first-page":"2141","article-title":"Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen","volume":"62","author":"Stabile","year":"2002","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1677\/ERC-08-0002","article-title":"Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma","volume":"15","author":"Hammoud","year":"2008","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Smida, T., Bruno, T.C., and Stabile, L.P. (2020). Influence of Estrogen on the NSCLC Microenvironment: A Comprehensive Picture and Clinical Implications. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00137"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"154298","DOI":"10.1016\/j.prp.2022.154298","article-title":"Expression patterns and clinical significance of estrogen receptor in non-small cell lung cancer","volume":"241","author":"Castellanos","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4238\/gmr.15038995","article-title":"Roles of ER\u03b1 and ER\u03b2 in estrogen-induced DDP chemoresistance in non-small cell lung cancer","volume":"15","author":"Yu","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5359","DOI":"10.1158\/1078-0432.CCR-09-0033","article-title":"Immunohistochemical expression of estrogen and progesterone receptors identifies a subset of NSCLCs and correlates with EGFR mutation","volume":"15","author":"Raso","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12967-019-2056-3","article-title":"Estrogen receptors promote NSCLC progression by modulating the membrane receptor signaling network: A systems biology perspective","volume":"17","author":"Gao","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_10","first-page":"2261","article-title":"Expression of Estrogen Receptor-alpha and Survival in Advanced-stage Non-small Cell Lung Cancer","volume":"38","author":"Scott","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1002\/ijc.21278","article-title":"Gender difference in estrogen receptor alpha promoter hypermethylation and its prognostic value in non-small cell lung cancer","volume":"117","author":"Lai","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41419-022-04514-4","article-title":"Estrogen receptor beta promotes lung cancer invasion via increasing CXCR4 expression","volume":"13","author":"Liu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"847","DOI":"10.4149\/neo_2018_181120N872","article-title":"Expression pattern of estrogen receptor \u03b2 and its correlation with multidrug resistance in non-small cell lung cancer","volume":"66","author":"Huang","year":"2019","journal-title":"Neoplasma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.21873\/anticanres.15012","article-title":"Estrogen Receptor \u03b2 Is Involved in Acquired Resistance to EGFR-tyrosine Kinase Inhibitors in Lung Cancer","volume":"41","author":"Sugiura","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s12276-023-01013-0","article-title":"Cancer-associated fibroblasts: From basic science to anticancer therapy","volume":"55","author":"Yang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.4161\/auto.25233","article-title":"Cytoprotective and nonprotective autophagy in cancer therapy","volume":"9","author":"Gewirtz","year":"2013","journal-title":"Autophagy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1159\/000346707","article-title":"Secretory versus degradative autophagy: Unconventional secretion of inflammatory mediators","volume":"5","author":"Jiang","year":"2013","journal-title":"J. Innate Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1080\/15548627.2019.1596479","article-title":"Autophagy-dependent secretion: Mechanism, factors secreted, and disease implications","volume":"15","author":"New","year":"2019","journal-title":"Autophagy"},{"key":"ref_19","first-page":"1","article-title":"Membrane Trafficking in Autophagy","volume":"336","author":"Neufeld","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12943-021-01423-6","article-title":"Crosstalk between autophagy inhibitors and endosome-related secretory pathways: A challenge for autophagy-based treatment of solid cancers","volume":"20","author":"Raudenska","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/s41419-020-03069-6","article-title":"Emerging role of the Hippo pathway in autophagy","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17848","DOI":"10.1073\/pnas.1908228116","article-title":"Cell phenotypic plasticity requires autophagic flux driven by YAP\/TAZ mechanotransduction","volume":"116","author":"Totaro","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Matarrese, P., Vona, R., Ascione, B., Cittadini, C., Tocci, A., and Mileo, A.M. (2023). Tumor Microenvironmental Cytokines Drive NSCLC Cell Aggressiveness and Drug-Resistance via YAP-Mediated Autophagy. Cells, 12.","DOI":"10.3390\/cells12071048"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1007\/s00109-024-02496-8","article-title":"Hypoxia drives estrogen receptor \u03b2-mediated cell growth via transcription activation in non-small cell lung cancer","volume":"102","author":"Su","year":"2024","journal-title":"J. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"50972","DOI":"10.18632\/oncotarget.8646","article-title":"Interaction between the human papillomavirus 16 E7 oncoprotein and gelsolin ignites cancer cell motility and invasiveness","volume":"7","author":"Matarrese","year":"2016","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hiramitsu, S., Ishikawa, T., Lee, W.R., Khan, T., Crumbley, C., Khwaja, N., Zamanian, F., Asghari, A., Sen, M., and Zhang, Y. (2018). Estrogen Receptor Beta-Mediated Modulation of Lung Cancer Cell Proliferation by 27-Hydroxycholesterol. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00470"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12935-024-03357-7","article-title":"PI3K\/AKT pathway as a pivotal regulator of epithelial-mesenchymal transition in lung tumor cells","volume":"24","author":"Moghbeli","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrclinonc.2017.44","article-title":"EMT, CSCs, and drug resistance: The mechanistic link and clinical implications","volume":"14","author":"Shibue","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_30","first-page":"1313","article-title":"Estrogen receptor \u03b21 activation accelerates resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer","volume":"39","author":"Fu","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1111\/cas.15770","article-title":"ELF1 suppresses autophagy to reduce cisplatin resistance via the miR-152-3p\/NCAM1\/ERK axis in lung cancer cells","volume":"114","author":"Zhao","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1002\/ijc.31398","article-title":"Targeting EGFR-mediated autophagy as a potential strategy for cancer therapy","volume":"143","author":"Sooro","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.1038\/s41467-018-07338-z","article-title":"Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap","volume":"9","author":"Lee","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1080\/15548627.2023.2210446","article-title":"Secretory autophagy-promoted cargo exocytosis requires active RAB37","volume":"20","author":"Wu","year":"2024","journal-title":"Autophagy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12929-022-00837-8","article-title":"Recent advances in conventional and unconventional vesicular secretion pathways in the tumor microenvironment","volume":"29","author":"Kuo","year":"2022","journal-title":"J. Biomed. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.me.27.020176.002041","article-title":"Estrogens and the human male","volume":"27","author":"Marcus","year":"1976","journal-title":"Annu. Rev. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Vicidomini, G. (2023). Current Challenges and Future Advances in Lung Cancer: Genetics, Instrumental Diagnosis and Treatment. Cancers, 15.","DOI":"10.3390\/cancers15143710"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.3394","article-title":"Microenvironmental regulation of tumor progression and metastasis","volume":"19","author":"Quail","year":"2013","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/hep.29678","article-title":"Actin cytoskeleton remodeling drives epithelial-mesenchymal transition for hepatoma invasion and metastasis in mice","volume":"67","author":"Peng","year":"2018","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1476-4598-8-109","article-title":"Antiproliferative effect of exemestane in lung cancer cells","volume":"8","author":"Koutras","year":"2009","journal-title":"Mol. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.genm.2010.10.002","article-title":"Sex differences in lung cancer susceptibility: A review","volume":"7","author":"Kiyohara","year":"2010","journal-title":"Gend. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/ijc.35309","article-title":"Estrogen, estrogen receptor and the tumor microenvironment of NSCLC","volume":"156","author":"Diao","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1158\/0008-5472.CAN-04-2694","article-title":"Regulation of endogenous gene expression in human non-small cell lung cancer cells by estrogen receptor ligands","volume":"65","author":"Hershberger","year":"2005","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Musial, C., Zaucha, R., Kuban-Jankowska, A., Konieczna, L., Belka, M., Marino Gammazza, A., Baczek, T., Cappello, F., Wozniak, M., and Gorska-Ponikowska, M. (2021). Plausible Role of Estrogens in Pathogenesis, Progression and Therapy of Lung Cancer. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18020648"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1257","DOI":"10.1038\/cddis.2013.428","article-title":"Systems biology of cisplatin resistance: Past, present and future","volume":"5","author":"Galluzzi","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/cr.2010.183","article-title":"NF-\u03baB and STAT3\u2014key players in liver inflammation and cancer","volume":"21","author":"He","year":"2011","journal-title":"Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/BF02967472","article-title":"Estrogen receptor-mediated cross-talk with growth factor signaling pathways","volume":"8","author":"Kato","year":"2001","journal-title":"Breast Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9575","DOI":"10.1038\/s41598-018-27810-6","article-title":"Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K\/AKT\/NF-\u03baB signaling","volume":"8","author":"Han","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41568-021-00344-2","article-title":"Autophagy in tumour immunity and therapy","volume":"21","author":"Xia","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Matarrese, P., Mattia, G., Pagano, M.T., Pontecorvi, G., Ortona, E., Malorni, W., and Car\u00e8, A. (2021). The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy. Cancers, 13.","DOI":"10.3390\/cancers13133287"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bustos, S.O., Antunes, F., Rangel, M.C., and Chammas, R. (2020). Emerging Autophagy Functions Shape the Tumor Microenvironment and Play a Role in Cancer Progression\u2014Implications for Cancer Therapy. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.606436"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/s41419-021-04150-4","article-title":"Autophagic secretion of HMGB1 from cancer-associated fibroblasts promotes metastatic potential of non-small cell lung cancer cells via NF\u03baB signaling","volume":"12","author":"Ren","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"118857","DOI":"10.1016\/j.bbamcr.2020.118857","article-title":"IKK\u03b2 activation promotes amphisome formation and extracellular vesicle secretion in tumor cells","volume":"1868","author":"Peng","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/tra.12878","article-title":"Inhibition of cholesterol transport impairs Cav-1 trafficking and small extracellular vesicles secretion, promoting amphisome formation in melanoma cells","volume":"24","author":"Peruzzu","year":"2023","journal-title":"Traffic"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2122053120","DOI":"10.1073\/pnas.2122053120","article-title":"17\u03b2-estradiol promotes extracellular vesicle release and selective miRNA loading in ER\u03b1-positive breast cancer","volume":"120","author":"Drula","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ejca.2021.10.032","article-title":"Failure to EGFR-TKI-based therapy and tumoural progression are promoted by MEOX2\/GLI1-mediated epigenetic regulation of EGFR in the human lung cancer","volume":"160","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.steroids.2016.05.008","article-title":"Prognostic relevance of estrogen receptor \u03b1, \u03b2 and aromatase expression in non-small cell lung cancer","volume":"113","author":"Skjefstad","year":"2016","journal-title":"Steroids"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1158\/1078-0432.CCR-10-0992","article-title":"Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome","volume":"17","author":"Stabile","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pinton, G., Thomas, W., Bellini, P., Manente, A.G., Favoni, R.E., Harvey, B.J., Mutti, L., and Moro, L. (2010). Estrogen receptor \u03b2 exerts tumor repressive functions in human malignant pleural mesothelioma via EGFR inactivation and affects response to gefitinib. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014110"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/ijc.34563","article-title":"ER\u03b2 promoted invadopodia formation-mediated non-small cell lung cancer metastasis via the ICAM1\/p-Src\/p-Cortactin signaling pathway","volume":"153","author":"Wang","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s13046-018-0804-5","article-title":"17\u03b2-estradiol upregulates IL6 expression through the ER\u03b2 pathway to promote lung adenocarcinoma progression","volume":"37","author":"Huang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.clbc.2022.06.004","article-title":"Immune Checkpoint Blockade in Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms and Future Perspectives","volume":"22","author":"Vathiotis","year":"2022","journal-title":"Clin. Breast Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nprot.2007.30","article-title":"In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro","volume":"2","author":"Liang","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.bbrc.2005.04.061","article-title":"Functional co-localization of monocytic aminopeptidase N\/CD13 with the Fc gamma receptors CD32 and CD64","volume":"331","author":"Riemann","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7490\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T04:26:58Z","timestamp":1787459218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":66,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167490"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167490","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}