FOS-Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8 + T Cells in Triple-Negative Breast Cancer.

Autor: Shu Y; Department of Breast Comprehensive Radiotherapy, Jiangxi Cancer Hospital, Nanchang, Jiangxi, People's Republic of China., Lan J; First Department of General Surgery, Jiangxi Gao'an People's Hospital, Gao'an, Jiangxi, People's Republic of China., Luo H; Department of Oncology, Taihe County People's Hospital, Ji'an, Jiangxi, People's Republic of China., Fu H; Department of Oncology, No.908 Hospital, Joint Logistics Support Force, Nanchang, Jiangxi, People's Republic of China., Xiao X; Department of Oncology, Taihe County Traditional Chinese Medicine Hospital, Ji'an, Jiangxi, People's Republic of China., Yang L; Department of Breast Surgery, Jiangxi Cancer Hospital, Nanchang, Jiangxi, People's Republic of China.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2025 Jan; Vol. 64 (1), pp. 162-175. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1002/mc.23834
Abstrakt: Radioresistance and immune evasion are interactive and crucial events leading to treatment failure and progression of human malignancies. This research studies the role of phospholipase C beta 1 (PLCB1) in these events in triple-negative breast cancer (TNBC) and the regulatory mechanism. PLCB1 was bioinformatically predicted as a dysregulated gene potentially linked to radioresistance in TNBC. Parental TNBC cell lines were exposed to fractionated radiation for 6 weeks. PLCB1 expression was decreased in the first 2 weeks but gradually increased from Week 3. PLCB1 knockdown increased the radiosensitivity of the cells, as manifested by a decreased half-inhibitory dose of irradiation, reduced cell proliferation, apoptosis resistance, mobility, and tumorigenesis in mice. The FOS transcription factor promoted PLCB1 transcription and activated the PI3K/AKT signaling. Knockdown of FOS similarly reduced radioresistance and T cells-mediated immune evasion. However, the radiosensitivity of TNBC cells and the antitumor effects of CD8 + T cells could be affected by a PI3K/AKT activator or by the PLCB1 upregulation. The PLCB1 or FOS knockdown also suppressed radioresistance and tumorigenesis of the TNBC cells in mice. In conclusion, FOS-mediated PLCB1 induces radioresistance and weakens the antitumor effects of CD8 + T cells in TNBC by activating the PI3K/AKT signaling pathway.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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