IL-33 stimulates the anticancer activities of eosinophils through extracellular vesicle-driven reprogramming of tumor cells.

Cancer Cell proliferation Eosinophils Epithelial to mesenchymal transition Extracellular vesicles IL-33 RNA sequencing Tumor microenvironment

Journal

Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647

Informations de publication

Date de publication:
27 Jul 2024
Historique:
received: 01 05 2024
accepted: 14 07 2024
medline: 27 7 2024
pubmed: 27 7 2024
entrez: 26 7 2024
Statut: epublish

Résumé

Immune cell-derived extracellular vesicles (EV) affect tumor progression and hold promise for therapeutic applications. Eosinophils are major effectors in Th2-related pathologies recently implied in cancer. Here, we evaluated the anti-tumor activities of eosinophil-derived EV following activation with the alarmin IL-33. We demonstrate that IL-33-activated mouse and human eosinophils produce higher quantities of EV with respect to eosinophils stimulated with IL-5. Following incorporation of EV from IL-33-activated eosinophils (Eo33-EV), but not EV from IL-5-treated eosinophils (Eo5-EV), mouse and human tumor cells increased the expression of cyclin-dependent kinase inhibitor (CDKI)-related genes resulting in cell cycle arrest in G0/G1, reduced proliferation and inhibited tumor spheroid formation. Moreover, tumor cells incorporating Eo33-EV acquired an epithelial-like phenotype characterized by E-Cadherin up-regulation, N-Cadherin downregulation, reduced cell elongation and migratory extent in vitro, and impaired capacity to metastasize to lungs when injected in syngeneic mice. RNA sequencing revealed distinct mRNA signatures in Eo33-EV and Eo5-EV with increased presence of tumor suppressor genes and enrichment in pathways related to epithelial phenotypes and negative regulation of cellular processes in Eo33-EV compared to Eo5-EV. Our studies underscore novel IL-33-stimulated anticancer activities of eosinophils through EV-mediated reprogramming of tumor cells opening perspectives on the use of eosinophil-derived EV in cancer therapy.

Identifiants

pubmed: 39061080
doi: 10.1186/s13046-024-03129-1
pii: 10.1186/s13046-024-03129-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

209

Informations de copyright

© 2024. The Author(s).

Références

Kalluri R, McAndrews KM. The role of extracellular vesicles in cancer. Cell. 2023;186:1610–26. https://doi.org/10.1016/j.cell.2023.03.010 .
doi: 10.1016/j.cell.2023.03.010 pubmed: 37059067 pmcid: 10484374
Wei H, Chen Q, Lin L, Sha C, Li T, Liu Y, Yin X, Xu Y, Chen L, Gao W, Li Y, et al. Regulation of exosome production and cargo sorting. Int J Biol Sci. 2021;17:163–77. https://doi.org/10.7150/ijbs.53671 .
doi: 10.7150/ijbs.53671 pubmed: 33390841 pmcid: 7757038
Gurung S, Perocheau D, Touramanidou L, Baruteau J. The exosome journey: from biogenesis to uptake and intracellular signalling. Cell Commun Signal. 2021;19:47. https://doi.org/10.1186/s12964-021-00730-1 .
doi: 10.1186/s12964-021-00730-1 pubmed: 33892745 pmcid: 8063428
Ginini L, Billan S, Fridman E, Gil Z. Insight into Extracellular Vesicle-Cell Communication: From Cell Recognition to Intracellular Fate. Cells. 2022;11(9):1375. https://doi.org/10.3390/cells11091375 .
doi: 10.3390/cells11091375 pubmed: 35563681 pmcid: 9101098
Wang S, Shi Y. Exosomes Derived from Immune Cells: The New Role of Tumor Immune Microenvironment and Tumor Therapy. Int J Nanomedicine. 2022;17:6527–50. https://doi.org/10.2147/IJN.S388604 .
doi: 10.2147/IJN.S388604 pubmed: 36575698 pmcid: 9790146
Wang X, Huang R, Lu Z, Wang Z, Chen X, Huang D. Exosomes from M1-polarized macrophages promote apoptosis in lung adenocarcinoma via the miR-181a-5p/ETS1/STK16 axis. Cancer Sci. 2022;113:986–1001. https://doi.org/10.1111/cas.15268 .
doi: 10.1111/cas.15268 pubmed: 35092121 pmcid: 8898733
Jiang H, Zhou L, Shen N, Ning X, Wu D, Jiang K, Huang X. M1 macrophage-derived exosomes and their key molecule lncRNA HOTTIP suppress head and neck squamous cell carcinoma progression by upregulating the TLR5/NF-κB pathway. Cell Death Dis. 2022;13:183. https://doi.org/10.1038/s41419-022-04640-z .
doi: 10.1038/s41419-022-04640-z pubmed: 35210436 pmcid: 8873565
Li X, Tang M. Exosomes released from M2 macrophages transfer miR-221-3p contributed to EOC progression through targeting CDKN1B. Cancer Med. 2020;9:5976–88. https://doi.org/10.1002/cam4.3252 .
doi: 10.1002/cam4.3252 pubmed: 32590883 pmcid: 7433826
Yin Z, Ma T, Huang B, Lin L, Zhou Y, Yan J, Zou Y, Chen S. Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF-β signaling pathway. J Exp Clin Cancer Res. 2019;38:310. https://doi.org/10.1186/s13046-019-1313-x .
doi: 10.1186/s13046-019-1313-x pubmed: 31307515 pmcid: 6631643
Mi X, Xu R, Hong S, Xu T, Zhang W, Liu M. M2 Macrophage-Derived Exosomal lncRNA AFAP1-AS1 and MicroRNA-26a Affect Cell Migration and Metastasis in Esophageal Cancer. Mol Ther Nucleic Acids. 2020;22:779–90. https://doi.org/10.1016/j.omtn.2020.09.035 .
doi: 10.1016/j.omtn.2020.09.035 pubmed: 33230475 pmcid: 7595846
Song L, Luan B, Xu Q, Shi R, Wang X. microRNA-155-3p delivered by M2 macrophages-derived exosomes enhances the progression of medulloblastoma through regulation of WDR82. J Transl Med. 2022;20:13. https://doi.org/10.1186/s12967-021-03156-y .
doi: 10.1186/s12967-021-03156-y pubmed: 34983581 pmcid: 8728908
Wu F, Xie M, Hun M, She Z, Li C, Luo S, Chen X, Wan W, Wen C, Tian J. Natural Killer Cell-Derived Extracellular Vesicles: Novel Players in Cancer Immunotherapy. Front Immunol. 2021;12: 658698. https://doi.org/10.3389/fimmu.2021.658698 .
doi: 10.3389/fimmu.2021.658698 pubmed: 34093547 pmcid: 8176011
Cai Z, Yang F, Yu L, Yu Z, Jiang L, Wang Q, Yang Y, Wang L, Cao X, Wang J. Activated T cell exosomes promote tumor invasion via Fas signaling pathway. J Immunol. 2012;188:5954–61. https://doi.org/10.4049/jimmunol.1103466 .
doi: 10.4049/jimmunol.1103466 pubmed: 22573809
Wang X, Xiang Z, Liu Y, Huang C, Pei Y, Zhi H, Wong WH, Wei H, Ng IO, Lee PP, Chan GC, et al. Exosomes derived from Vδ2-T cells control Epstein-Barr virus-associated tumors and induce T cell antitumor immunity. Sci Transl Med. 2020;12(563):eaaz3426. https://doi.org/10.1126/scitranslmed.aaz3426 .
doi: 10.1126/scitranslmed.aaz3426 pubmed: 32998970
Li L, Lu S, Liang X, Cao B, Wang S, Jiang J, Luo H, He S, Lang J, Zhu G. γδTDEs: An Efficient Delivery System for miR-138 with Anti-tumoral and Immunostimulatory Roles on Oral Squamous Cell Carcinoma. Mol Ther Nucleic Acids. 2019;14:101–13. https://doi.org/10.1016/j.omtn.2018.11.009 .
doi: 10.1016/j.omtn.2018.11.009 pubmed: 30594069
Yang Z, Wang W, Zhao L, Wang X, Gimple RC, Xu L, Wang Y, Rich JN, Zhou S. Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs. Sci Adv. 2021;7(9):eabb0737. https://doi.org/10.1126/sciadv.abb0737 .
doi: 10.1126/sciadv.abb0737 pubmed: 33627414 pmcid: 7904265
Munich S, Sobo-Vujanovic A, Buchser WJ, Beer-Stolz D, Vujanovic NL. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology. 2012;1:1074–83. https://doi.org/10.4161/onci.20897 .
doi: 10.4161/onci.20897 pubmed: 23170255 pmcid: 3494621
Xiao H, Lässer C, Shelke GV, Wang J, Rådinger M, Lunavat TR, Malmhäll C, Lin LH, Li J, Li L, Lötvall J. Mast cell exosomes promote lung adenocarcinoma cell proliferation - role of KIT-stem cell factor signaling. Cell Commun Signal. 2014;12:64. https://doi.org/10.1186/s12964-014-0064-8 .
doi: 10.1186/s12964-014-0064-8 pubmed: 25311367 pmcid: 4206705
Varricchi G, Galdiero MR, Loffredo S, Lucarini V, Marone G, Mattei F, Marone G, Schiavoni G. Eosinophils: The unsung heroes in cancer? OncoImmunology. 2018;7(2):e1393134. https://doi.org/10.1080/2162402X.2017.1393134 .
doi: 10.1080/2162402X.2017.1393134 pubmed: 29308325
Mattei F, Andreone S, Marone G, Gambardella AR, Loffredo S, Varricchi G, Schiavoni G. Eosinophils in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1273:1–28. https://doi.org/10.1007/978-3-030-49270-0_1 .
doi: 10.1007/978-3-030-49270-0_1 pubmed: 33119873
Andreone S, Spadaro F, Buccione C, Mancini J, Tinari A, Sestili P, Gambardella AR, Lucarini V, Ziccheddu G, Parolini I, Zanetti C, et al. IL-33 Promotes CD11b/CD18-Mediated Adhesion of Eosinophils to Cancer Cells and Synapse-Polarized Degranulation Leading to Tumor Cell Killing. Cancers (Basel). 2019;11(11):1664. https://doi.org/10.3390/cancers11111664 .
doi: 10.3390/cancers11111664 pubmed: 31717819
Lucarini V, Ziccheddu G, Macchia I, La Sorsa V, Peschiaroli F, Buccione C, Sistigu A, Sanchez M, Andreone S, D’Urso MT, Spada M, et al. IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils. OncoImmunology. 2017;6(6):e1317420. https://doi.org/10.1080/2162402X.2017.1317420
doi: 10.1080/2162402X.2017.1317420 pubmed: 28680750 pmcid: 5486175
Kienzl M, Hasenoehrl C, Valadez-Cosmes P, Maitz K, Sarsembayeva A, Sturm E, Heinemann A, Kargl J, Schicho R. IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils. Oncoimmunology. 2020;9(1):1776059. https://doi.org/10.1080/2162402X.2020.1776059 .
doi: 10.1080/2162402X.2020.1776059 pubmed: 32923137 pmcid: 7458617
Reichman H, Itan M, Rozenberg P, Yarmolovski T, Brazowski E, Varol C, Gluck N, Shapira S, Arber N, Qimron U, Karo-Atar D, et al. Activated Eosinophils Exert Antitumorigenic Activities in Colorectal Cancer. Cancer Immunol Res. 2019;7:388–400. https://doi.org/10.1158/2326-6066.CIR-18-0494 .
doi: 10.1158/2326-6066.CIR-18-0494 pubmed: 30665890
Gatault S, Legrand F, Delbeke M, Loiseau S, Capron M. Involvement of eosinophils in the anti-tumor response. Cancer Immunol Immunother. 2012;61:1527–34. https://doi.org/10.1007/s00262-012-1288-3 .
doi: 10.1007/s00262-012-1288-3 pubmed: 22706380 pmcid: 11029779
Legrand F, Driss V, Delbeke M, Loiseau S, Hermann E, Dombrowicz D, Capron M. Human eosinophils exert TNF-α and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. J Immunol. 2010;185:7443–51. https://doi.org/10.4049/jimmunol.1000446 .
doi: 10.4049/jimmunol.1000446 pubmed: 21068403
Munitz A, Bachelet I, Fraenkel S, Katz G, Mandelboim O, Simon HU, Moretta L, Colonna M, Levi-Schaffer F. 2B4 (CD244) is expressed and functional on human eosinophils. J Immunol. 2005;174:110–8.
doi: 10.4049/jimmunol.174.1.110 pubmed: 15611233
Hollande C, Boussier J, Ziai J, Nozawa T, Bondet V, Phung W, Lu B, Duffy D, Paradis V, Mallet V, Eberl G, et al. Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nat Immunol. 2019;20:257–64. https://doi.org/10.1038/s41590-019-0321-5 .
doi: 10.1038/s41590-019-0321-5 pubmed: 30778250
Mazzeo C, Cañas JA, Zafra MP, Rojas Marco A, Fernández-Nieto M, Sanz V, Mittelbrunn M, Izquierdo M, Baixaulli F, Sastre J, Del Pozo V. Exosome secretion by eosinophils: A possible role in asthma pathogenesis. J Allergy Clin Immunol. 2015;135:1603–13. https://doi.org/10.1016/j.jaci.2014.11.026 .
doi: 10.1016/j.jaci.2014.11.026 pubmed: 25617225
Cañas JA, Sastre B, Mazzeo C, Fernández-Nieto M, Rodrigo-Muñoz JM, González-Guerra A, Izquierdo M, Barranco P, Quirce S, Sastre J, Del Pozo V. Exosomes from eosinophils autoregulate and promote eosinophil functions. J Leukoc Biol. 2017;101:1191–9. https://doi.org/10.1189/jlb.3AB0516-233RR .
doi: 10.1189/jlb.3AB0516-233RR pubmed: 28096299
Cañas JA, Sastre B, Rodrigo-Muñoz JM, Fernández-Nieto M, Barranco P, Quirce S, Sastre J, Del Pozo V. Eosinophil-derived exosomes contribute to asthma remodelling by activating structural lung cells. Clin Exp Allergy. 2018;48:1173–85. https://doi.org/10.1111/cea.13122 .
doi: 10.1111/cea.13122 pubmed: 29451337
Cañas JA, Rodrigo-Muñoz JM, Del Pozo V. Isolation and Functional Aspects of Eosinophil-Derived Exosomes. Methods Mol Biol. 2021;2241:149–59. https://doi.org/10.1007/978-1-0716-1095-4_13 .
doi: 10.1007/978-1-0716-1095-4_13 pubmed: 33486735
Coscia C, Parolini I, Sanchez M, Biffoni M, Boussadia Z, Zanetti C, Fiani ML, Sargiacomo M. Generation, Quantification, and Tracing of Metabolically Labeled Fluorescent Exosomes. Methods Mol Biol. 2016;1448:217–35. https://doi.org/10.1007/978-1-4939-3753-0_16 .
doi: 10.1007/978-1-4939-3753-0_16 pubmed: 27317184
Barreca V, Boussadia Z, Polignano D, Galli L, Tirelli V, Sanchez M, Falchi M, Bertuccini L, Iosi F, Tatti M, Sargiacomo M, et al. Metabolic labelling of a subpopulation of small extracellular vesicles using a fluorescent palmitic acid analogue. J Extracell Vesicles. 2023;12: e12392. https://doi.org/10.1002/jev2.12392 .
doi: 10.1002/jev2.12392 pubmed: 38072803
De Ninno A, Bertani FR, Gerardino A, Schiavoni G, Musella M, Galassi C, Mattei F, Sistigu A, Businaro L. Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments. J Vis Exp. 2021. https://doi.org/10.3791/61895 .
doi: 10.3791/61895 pubmed: 33999026
Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285:17442–52. https://doi.org/10.1074/jbc.M110.107821 .
doi: 10.1074/jbc.M110.107821 pubmed: 20353945 pmcid: 2878508
Boussadia Z, Lamberti J, Mattei F, Pizzi E, Puglisi R, Zanetti C, Pasquini L, Fratini F, Fantozzi L, Felicetti F, Fecchi K, et al. Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules. J Exp Clin Cancer Res. 2018;37:245. https://doi.org/10.1186/s13046-018-0915-z .
doi: 10.1186/s13046-018-0915-z pubmed: 30290833 pmcid: 6173926
Andreone S, Gambardella AR, Mancini J, Loffredo S, Marcella S, La Sorsa V, Varricchi G, Schiavoni G, Mattei F. Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight. Front Immunol. 2020;11: 571593. https://doi.org/10.3389/fimmu.2020.571593 .
doi: 10.3389/fimmu.2020.571593 pubmed: 33329534 pmcid: 7734277
Carretero R, Sektioglu IM, Garbi N, Salgado OC, Beckhove P, Hämmerling GJ. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol. 2015;16:609–17. https://doi.org/10.1038/ni.3159 .
doi: 10.1038/ni.3159 pubmed: 25915731
Efraim NB, A.H., and Levi-Schaffer, F. Roles of eosinophils in the modulation of angiogenesis. Chem Immunol Allergy. 2014;99:138–54. https://doi.org/10.1159/000353251 .
doi: 10.1159/000353251
Akuthota P, Carmo LA, Bonjour K, Murphy RO, Silva TP, Gamalier JP, Capron KL, Tigges J, Toxavidis V, Camacho V, Ghiran I, et al. Extracellular Microvesicle Production by Human Eosinophils Activated by “Inflammatory” Stimuli. Front Cell Dev Biol. 2016;4:117. https://doi.org/10.3389/fcell.2016.00117 .
doi: 10.3389/fcell.2016.00117 pubmed: 27833910 pmcid: 5081571
Leal-Esteban LC, Fajas L. Cell cycle regulators in cancer cell metabolism. Biochim Biophys Acta Mol Basis Dis. 2020;1866: 165715. https://doi.org/10.1016/j.bbadis.2020.165715 .
doi: 10.1016/j.bbadis.2020.165715 pubmed: 32035102
Gatault S, Delbeke M, Driss V, Sarazin A, Dendooven A, Kahn JE, Lefèvre G, Capron M. IL-18 Is Involved in Eosinophil-Mediated Tumoricidal Activity against a Colon Carcinoma Cell Line by Upregulating LFA-1 and ICAM-1. J Immunol. 2015;195:2483–92. https://doi.org/10.4049/jimmunol.1402914 .
doi: 10.4049/jimmunol.1402914 pubmed: 26216891
Loh CY, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, Chong PP, Looi CY. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells. 2019;8(10):1118. https://doi.org/10.3390/cells8101118 .
doi: 10.3390/cells8101118 pubmed: 31547193 pmcid: 6830116
Garcia MA, Nelson WJ, Chavez N. Cell-Cell Junctions Organize Structural and Signaling Networks. Cold Spring Harb Perspect Biol. 2018;10(4):a029181. https://doi.org/10.1101/cshperspect.a029181 .
doi: 10.1101/cshperspect.a029181 pubmed: 28600395 pmcid: 5773398
Campbell K. Contribution of epithelial-mesenchymal transitions to organogenesis and cancer metastasis. Curr Opin Cell Biol. 2018;55:30–5. https://doi.org/10.1016/j.ceb.2018.06.008 .
doi: 10.1016/j.ceb.2018.06.008 pubmed: 30006053 pmcid: 6284102
Mittal V. Epithelial Mesenchymal Transition in Tumor Metastasis. Annu Rev Pathol. 2018;13:395–412. https://doi.org/10.1146/annurev-pathol-020117-043854 .
doi: 10.1146/annurev-pathol-020117-043854 pubmed: 29414248
Ocaña OH, Córcoles R, Fabra A, Moreno-Bueno G, Acloque H, Vega S, Barrallo-Gimeno A, Cano A, Nieto MA. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell. 2012;22:709–24. https://doi.org/10.1016/j.ccr.2012.10.012 .
doi: 10.1016/j.ccr.2012.10.012 pubmed: 23201163
Tran HD, Luitel K, Kim M, Zhang K, Longmore GD, Tran DD. Transient SNAIL1 expression is necessary for metastatic competence in breast cancer. Cancer Res. 2014;74:6330–40. https://doi.org/10.1158/0008-5472.CAN-14-0923 .
doi: 10.1158/0008-5472.CAN-14-0923 pubmed: 25164016 pmcid: 4925010
Stankic M, Pavlovic S, Chin Y, Brogi E, Padua D, Norton L, Massagué J, Benezra R. TGF-β-Id1 signaling opposes Twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition. Cell Rep. 2013;5:1228–42. https://doi.org/10.1016/j.celrep.2013.11.014 .
doi: 10.1016/j.celrep.2013.11.014 pubmed: 24332369 pmcid: 3891470
Veloso ES, de Carvalho BA, de Souza Silva FH, Ribeiro TS, Lima BM, Almeida CP, da Silva VHSR, Rocha SA, de Araújo Campos MR, Del Puerto HL, Ferreira E. Epithelial-mesenchymal transition inhibition by metformin reduces melanoma lung metastasis in a murine model. Sci Rep. 2022;12:17776. https://doi.org/10.1038/s41598-022-22235-8 .
doi: 10.1038/s41598-022-22235-8 pubmed: 36273071 pmcid: 9588059
Lim JCW, Kwan YP, Tan MS, Teo MHY, Chiba S, Wahli W, Wang X. The Role of PPARβ/δ in Melanoma Metastasis. Int J Mol Sci. 2018;19(10):2860. https://doi.org/10.3390/ijms19102860 .
doi: 10.3390/ijms19102860 pubmed: 30241392 pmcid: 6213649
Tian L, Li L, Xing W, Li R, Pei C, Dong X, Fu Y, Gu C, Guo X, Jia Y, Wang G, et al. IRGM1 enhances B16 melanoma cell metastasis through PI3K-Rac1 mediated epithelial mesenchymal transition. Sci Rep. 2015;5:12357. https://doi.org/10.1038/srep12357 .
doi: 10.1038/srep12357 pubmed: 26202910 pmcid: 4512008
Revenco T, Nicodème A, Pastushenko I, Sznurkowska MK, Latil M, Sotiropoulou PA, Dubois C, Moers V, Lemaire S, de Maertelaer V, Blanpain C. Context Dependency of Epithelial-to-Mesenchymal Transition for Metastasis. Cell Rep. 2019;29:1458–1468.e1453. https://doi.org/10.1016/j.celrep.2019.09.081 .
doi: 10.1016/j.celrep.2019.09.081 pubmed: 31693888
Oh TI, Lee M, Lee YM, Kim GH, Lee D, You JS, Kim SH, Choi M, Jang H, Park YM, Shin HW, et al. PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition. Cancers (Basel). 2021;13(8):1772. https://doi.org/10.3390/cancers13081772 .
doi: 10.3390/cancers13081772 pubmed: 33917757 pmcid: 8068195
Berr AL, Wiese K, Dos Santos G, Koch CM, Anekalla KR, Kidd M, Davis JM, Cheng Y, Hu YS, Ridge KM. Vimentin is required for tumor progression and metastasis in a mouse model of non-small cell lung cancer. Oncogene. 2023;42:2074–87. https://doi.org/10.1038/s41388-023-02703-9 .
doi: 10.1038/s41388-023-02703-9 pubmed: 37161053 pmcid: 10275760
Lee MS, Lee J, Kim YM, Lee H. The metastasis suppressor CD82/KAI1 represses the TGF-β. Prostate. 2019;79:1400–11. https://doi.org/10.1002/pros.23837 .
doi: 10.1002/pros.23837 pubmed: 31212375
Cai YJ, Ma B, Wang ML, Chen J, Zhao FG, Zhou JD, Guo X, Zheng L, Xu CJ, Wang Y, He YB, et al. Impact of Nischarin on EMT regulators in breast cancer cell lines. Oncol Lett. 2020;20:291. https://doi.org/10.3892/ol.2020.12154 .
doi: 10.3892/ol.2020.12154 pubmed: 33101485 pmcid: 7576990
Maziveyi M, Dong S, Baranwal S, Mehrnezhad A, Rathinam R, Huckaba TM, Mercante DE, Park K, Alahari SK. Exosomes from Nischarin-Expressing Cells Reduce Breast Cancer Cell Motility and Tumor Growth. Cancer Res. 2019;79:2152–66. https://doi.org/10.1158/0008-5472.CAN-18-0842 .
doi: 10.1158/0008-5472.CAN-18-0842 pubmed: 30635277 pmcid: 7204893
Bereczki O, Ujfaludi Z, Pardi N, Nagy Z, Tora L, Boros IM, Balint E. TATA binding protein associated factor 3 (TAF3) interacts with p53 and inhibits its function. BMC Mol Biol. 2008;9:57. https://doi.org/10.1186/1471-2199-9-57 .
doi: 10.1186/1471-2199-9-57 pubmed: 18549481 pmcid: 2441632
Seo J, Lozano MM, Dudley JP. Nuclear matrix binding regulates SATB1-mediated transcriptional repression. J Biol Chem. 2005;280:24600–9. https://doi.org/10.1074/jbc.M414076200 .
doi: 10.1074/jbc.M414076200 pubmed: 15851481
Hill AA, Riley PR. Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by the cofactor FHL2. Mol Cell Biol. 2004;24:9835–47. https://doi.org/10.1128/MCB.24.22.9835-9847.2004 .
doi: 10.1128/MCB.24.22.9835-9847.2004 pubmed: 15509787 pmcid: 525463
Oshima M, Mimura J, Sekine H, Okawa H, Fujii-Kuriyama Y. SUMO modification regulates the transcriptional repressor function of aryl hydrocarbon receptor repressor. J Biol Chem. 2009;284:11017–26. https://doi.org/10.1074/jbc.M808694200 .
doi: 10.1074/jbc.M808694200 pubmed: 19251700 pmcid: 2670107
Carpenter B, Hill KJ, Charalambous M, Wagner KJ, Lahiri D, James DI, Andersen JS, Schumacher V, Royer-Pokora B, Mann M, Ward A, et al. BASP1 is a transcriptional cosuppressor for the Wilms’ tumor suppressor protein WT1. Mol Cell Biol. 2004;24:537–49. https://doi.org/10.1128/MCB.24.2.537-549.2004 .
doi: 10.1128/MCB.24.2.537-549.2004 pubmed: 14701728 pmcid: 343806
Wong DT, Kim JJ, Khalid O, Sun HH, Kim Y. Double edge: CDK2AP1 in cell-cycle regulation and epigenetic regulation. J Dent Res. 2012;91:235–41. https://doi.org/10.1177/0022034511420723 .
doi: 10.1177/0022034511420723 pubmed: 21865592 pmcid: 3275332
Sampson C, Wang Q, Otkur W, Zhao H, Lu Y, Liu X, Piao HL. The roles of E3 ubiquitin ligases in cancer progression and targeted therapy. Clin Transl Med. 2023;13: e1204. https://doi.org/10.1002/ctm2.1204 .
doi: 10.1002/ctm2.1204 pubmed: 36881608 pmcid: 9991012
Zhao BW, Sun SM, Xu K, Li YY, Lei WL, Li L, Liu SL, Ouyang YC, Sun QY, Wang ZB. FBXO34 Regulates the G2/M Transition and Anaphase Entry in Meiotic Oocytes. Front Cell Dev Biol. 2021;9: 647103. https://doi.org/10.3389/fcell.2021.647103 .
doi: 10.3389/fcell.2021.647103 pubmed: 33842473 pmcid: 8027338
Li H, Zhang P, Liu C, Wang Y, Deng Y, Dong W, Yu Y. The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases. Cells. 2022;12(1):8. https://doi.org/10.3390/cells12010008 .
doi: 10.3390/cells12010008 pubmed: 36611803 pmcid: 9818648
Hulea L, Nepveu A. CUX1 transcription factors: from biochemical activities and cell-based assays to mouse models and human diseases. Gene. 2012;497:18–26. https://doi.org/10.1016/j.gene.2012.01.039 .
doi: 10.1016/j.gene.2012.01.039 pubmed: 22306263
Cheng Z, Wei W, Wu Z, Wang J, Ding X, Sheng Y, Han Y, Wu Q. ARPC2 promotes breast cancer proliferation and metastasis. Oncol Rep. 2019;41:3189–200. https://doi.org/10.3892/or.2019.7113 .
doi: 10.3892/or.2019.7113 pubmed: 31002363 pmcid: 6488984
Kim SY, Dunn IF, Firestein R, Gupta P, Wardwell L, Repich K, Schinzel AC, Wittner B, Silver SJ, Root DE, Boehm JS, et al. CK1epsilon is required for breast cancers dependent on beta-catenin activity. PLoS ONE. 2010;5: e8979. https://doi.org/10.1371/journal.pone.0008979 .
doi: 10.1371/journal.pone.0008979 pubmed: 20126544 pmcid: 2813871
Grisaru-Tal S, Dulberg S, Beck L, Zhang C, Itan M, Hediyeh-Zadeh S, Caldwell J, Rozenberg P, Dolitzky A, Avlas S, Hazut I, et al. Metastasis-Entrained Eosinophils Enhance Lymphocyte-Mediated Antitumor Immunity. Cancer Res. 2021;81:5555–71. https://doi.org/10.1158/0008-5472.CAN-21-0839 .
doi: 10.1158/0008-5472.CAN-21-0839 pubmed: 34429328
Jung I, Shin S, Baek MC, Yea K. Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications. Exp Mol Med. 2024;56:19–31. https://doi.org/10.1038/s12276-023-01132-8 .
doi: 10.1038/s12276-023-01132-8 pubmed: 38172594 pmcid: 10834411

Auteurs

Adriana Rosa Gambardella (AR)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Caterina Antonucci (C)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Cristiana Zanetti (C)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Francesco Noto (F)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Sara Andreone (S)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Davide Vacca (D)

Tumor Immunology Unit, Department of Sciences for Health Promotion and Mother-Child Care "G. D'Alessandro", University of Palermo, Palermo, 90127, Italy.

Valentina Pellerito (V)

Tumor Immunology Unit, Department of Sciences for Health Promotion and Mother-Child Care "G. D'Alessandro", University of Palermo, Palermo, 90127, Italy.

Chiara Sicignano (C)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Giuseppe Parrottino (G)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Valentina Tirelli (V)

Core Facilities, Istituto Superiore Di Sanità, Rome, Italy.

Antonella Tinari (A)

National Center for Gender Medicine, Istituto Superiore Di Sanità, Rome, Italy.

Mario Falchi (M)

National AIDS Center, Istituto Superiore Di Sanità, Rome, Italy.

Adele De Ninno (A)

CNR-IFN Institute for Photonics and Nanotechnologies, Rome, Italy.

Luca Businaro (L)

CNR-IFN Institute for Photonics and Nanotechnologies, Rome, Italy.

Stefania Loffredo (S)

Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
World Allergy Organization (WAO), Center of Excellence (CoE), Naples, 80131, Italy.
Institute of Experimental Endocrinology and Oncology, National Research Council (CNR), Naples, 80131, Italy.

Gilda Varricchi (G)

Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
World Allergy Organization (WAO), Center of Excellence (CoE), Naples, 80131, Italy.
Institute of Experimental Endocrinology and Oncology, National Research Council (CNR), Naples, 80131, Italy.

Claudio Tripodo (C)

Tumor Immunology Unit, Department of Sciences for Health Promotion and Mother-Child Care "G. D'Alessandro", University of Palermo, Palermo, 90127, Italy.

Claudia Afferni (C)

National Center for Drug Research and Evaluation, Istituto Superiore Di Sanità, Rome, Italy.

Isabella Parolini (I)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.
Laboratory of Molecular Medicine and DNA Repair, Department of Medicine, University of Udine, Udine, Italy.

Fabrizio Mattei (F)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy. fabrizio.mattei@iss.it.

Giovanna Schiavoni (G)

Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy. giovanna.schiavoni@iss.it.

Classifications MeSH