NAC1 promotes stemness and regulates myeloid-derived cell status in triple-negative breast cancer.
Triple Negative Breast Neoplasms
/ pathology
Humans
Animals
Neoplastic Stem Cells
/ metabolism
Female
Mice
Myeloid-Derived Suppressor Cells
/ metabolism
Cell Proliferation
Repressor Proteins
/ metabolism
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Tumor Microenvironment
Prognosis
Cell Movement
Killer Cells, Natural
/ metabolism
Neoplasm Proteins
Cancer stem cells
MDSCs
NAC1
NK cells
TME
TNBC
Journal
Molecular cancer
ISSN: 1476-4598
Titre abrégé: Mol Cancer
Pays: England
ID NLM: 101147698
Informations de publication
Date de publication:
06 Sep 2024
06 Sep 2024
Historique:
received:
02
02
2024
accepted:
27
08
2024
medline:
7
9
2024
pubmed:
7
9
2024
entrez:
6
9
2024
Statut:
epublish
Résumé
Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated protein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Additionally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFβ, IL-6). Intriguingly, the impact of NAC1 on tumor growth varies with the host immune status, showing diminished tumorigenicity in natural killer (NK) cell-competent mice but increased tumorigenicity in NK cell-deficient ones. This highlights the important role of the host immune system in TNBC progression. In addition, high NAC1 level in MDSCs also supports TNBC stemness. Together, this study implies NAC1 as a promising therapeutic target able to simultaneously eradicate CSCs and mitigate immune evasion.
Identifiants
pubmed: 39243032
doi: 10.1186/s12943-024-02102-y
pii: 10.1186/s12943-024-02102-y
doi:
Substances chimiques
Repressor Proteins
0
NACC1 protein, human
0
Neoplasm Proteins
0
Types de publication
Letter
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
188Subventions
Organisme : NCI NIH HHS
ID : R01CA221867
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA221867
Pays : United States
Organisme : Susan G. Komen Foundation
ID : CCR18548501
Organisme : NIH HHS
ID : P20GM121327
Pays : United States
Informations de copyright
© 2024. The Author(s).
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