TY - JOUR
T1 - NAC1 promotes stemness and regulates myeloid-derived cell status in triple-negative breast cancer
AU - Ngule, Chrispus
AU - Shi, Ruyi
AU - Ren, Xingcong
AU - Jia, Hongyan
AU - Oyelami, Felix
AU - Li, Dong
AU - Park, Younhee
AU - Kim, Jinhwan
AU - Hemati, Hami
AU - Zhang, Yi
AU - Xiong, Xiaofang
AU - Shinkle, Andrew
AU - Vanderford, Nathan L.
AU - Bachert, Sara
AU - Zhou, Binhua P.
AU - Wang, Jianlong
AU - Song, Jianxun
AU - Liu, Xia
AU - Yang, Jin Ming
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - Cancer stem cells
KW - MDSCs
KW - NAC1
KW - NK cells
KW - TME
KW - TNBC
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UR - http://www.scopus.com/inward/citedby.url?scp=85203272916&partnerID=8YFLogxK
U2 - 10.1186/s12943-024-02102-y
DO - 10.1186/s12943-024-02102-y
M3 - Article
C2 - 39243032
AN - SCOPUS:85203272916
SN - 1476-4598
VL - 23
JO - Molecular Cancer
JF - Molecular Cancer
IS - 1
M1 - 188
ER -
