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Unconventional p65/p52 NF-κB module regulates key tumor microenvironment-related genes in breast tumor-associated macrophages (TAMs).
De Paolis, Veronica; Troisi, Virginia; Bordin, Antonella; Pagano, Francesca; Caputo, Viviana; Parisi, Chiara.
Afiliação
  • De Paolis V; Institute of Biochemistry and Cell Biology, CNR-National Research Council, Via Ercole Ramarini, 32, 00015 Monterotondo Scalo, RM, Italy. Electronic address: veronica.depaolis@ibbc.cnr.it.
  • Troisi V; Institute of Biochemistry and Cell Biology, CNR-National Research Council, Via Ercole Ramarini, 32, 00015 Monterotondo Scalo, RM, Italy.
  • Bordin A; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica, 79, 04100, Latina, Italy.
  • Pagano F; Institute of Biochemistry and Cell Biology, CNR-National Research Council, Via Ercole Ramarini, 32, 00015 Monterotondo Scalo, RM, Italy.
  • Caputo V; Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy.
  • Parisi C; Institute of Biochemistry and Cell Biology, CNR-National Research Council, Via Ercole Ramarini, 32, 00015 Monterotondo Scalo, RM, Italy. Electronic address: chiara.parisi@cnr.it.
Life Sci ; 357: 123059, 2024 Nov 15.
Article em En | MEDLINE | ID: mdl-39278618
ABSTRACT
The complex heterogeneity of tumor microenvironment (TME) of triple-negative breast cancer (TNBC) presents a significant obstacle to cytotoxic immune response and successful treatment, building up one of the most hostile oncological phenotypes. Among the most abundant TME components, tumor-associated macrophages (TAMs) have pivotal pro-tumoral functions, involving discordant roles for the nuclear factor kappa-B (NF-κB) transcription factors and directing to higher levels of pathway complexity. In both resting macrophages and TAMs, we recently revealed the existence of the uncharacterized NF-κB p65/p52 dimer. In the present study, we demonstrated its enhanced active nuclear localization in TAMs and validated selected immune target genes as directly regulated by dimer binding on DNA sequences. We demonstrated by ChIP-qPCR that p65/p52 enrichment on HSPG2 and CSF-1 regulatory regions is strictly dependent on macrophage polarization and tumor environment. Our data provide novel mechanisms of transcriptional regulation in TAMs, orchestrated by the varied and dynamic nature of NF-κB combinations, which needs to be considered when targeting this pathway in cancer therapies. Our results offer p65/p52, together with identified regulatory regions on genes impacting macrophage behavior and tumor biology, as novel molecular targets for TNBC, aimed at modulating TAMs functions towards anti-tumoral phenotypes and thus improving cancer treatment outcomes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação Neoplásica da Expressão Gênica / Fator de Transcrição RelA / Microambiente Tumoral / Neoplasias de Mama Triplo Negativas / Macrófagos Associados a Tumor Limite: Female / Humans Idioma: En Revista: Life Sci Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação Neoplásica da Expressão Gênica / Fator de Transcrição RelA / Microambiente Tumoral / Neoplasias de Mama Triplo Negativas / Macrófagos Associados a Tumor Limite: Female / Humans Idioma: En Revista: Life Sci Ano de publicação: 2024 Tipo de documento: Article