NUCB2 inhibition antagonizes osteosarcoma progression and promotes anti-tumor immunity through inactivating NUCKS1/CXCL8 axis.

Autor: Ji R; The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116044, China., Wang Y; The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116044, China., Pan D; The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116044, China., Han J; Dalian NO.3 People's Hospital, Department of Orthopedics, Dalian, Liaoning 116044, China., Wang Y; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning 116044, China., Zheng S; The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116044, China., Zhao W; The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116044, China. Electronic address: drzwz@163.com., Li X; College of Stomatology Dalian Medical University, Dalian 116044, China. Electronic address: xiaojieli0504@dmu.edu.cn., Han C; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning 116044, China. Electronic address: hanchuanchun@163.com., Zhang L; The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116044, China. Electronic address: zhanglu_dalian@163.com.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2024 Jun 01; Vol. 591, pp. 216893. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1016/j.canlet.2024.216893
Abstrakt: The oncogenic properties of Nucleobindin2 (NUCB2) have been observed in various cancer types. Nevertheless, the precise understanding of the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma remains limited. This investigation reported that NUCB2 was significantly increased upon glucose deprivation-induced metabolic stress. Elevated NUCB2 suppressed glucose deprivation-induced cell death and reactive oxygen species (ROS) increase. Depletion of NUCB2 resulted in a reduction in osteosarcoma cell proliferation as well as metastatic potential in vitro and in vivo. Mechanically, NUCB2 ablation suppressed C-X-C Motif Chemokine Ligand 8 (CXCL8) expression which then reduced programmed cell death 1 ligand 1 (PD-L1) expression and stimulated anti-tumor immunity mediated through cytotoxic T cells. Importantly, a combination of NUCB2 depletion with anti-PD-L1 treatment improved anti-tumor T-cell immunity in vivo. Moreover, we further demonstrated that NUCB2 interacted with NUCKS1 to inhibit its degradation, which is responsible for the transcriptional regulation of CXCL8 expression. Altogether, the outcome emphasizes the function of NUCB2 in osteosarcoma and indicates that NUCB2 elevates osteosarcoma progression and immunosuppressive microenvironment through the NUCKS1/CXCL8 pathway.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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