Detoxified pneumolysin derivative ΔA146Ply inhibits triple- negative breast cancer metastasis mainly via mannose receptor-mediated autophagy inhibition.

IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Virulence Pub Date : 2024-12-01 Epub Date: 2024-09-26 DOI:10.1080/21505594.2023.2283898
Hong Zhang, Tao Zhu, Wenchun Xu, Bichen Liu, Kaifeng Wu, Yibing Yin, Xuemei Zhang
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Abstract

The detoxified pneumolysin derivative ΔA146Ply has been proven to have a direct anti-triple negative breast cancer effect by our group, but its work model remains unclear. In this study, we focused on its ability to inhibit triple-negative breast cancer metastasis. We found that ΔA146Ply suppressed the migration and invasion of triple-negative breast cancer cells by activating mannose receptor and toll-like receptor 4. Their activation triggers the activation of the mammalian target of rapamycin signalling, sequentially leading to autophagy, transforming growth factor-β1, and epithelial-mesenchymal transition inhibition. Furthermore, the combination of doxorubicin and ΔA146Ply significantly inhibited triple-negative breast cancer progression and prolonged survival in tumour-bearing mice. Taken together, our study provides an alternative microbiome-based mannose receptor-targeted therapy for triple-negative breast cancer and a novel theoretical and experimental basis for the downstream signalling pathway of the mannose receptor.

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解毒溶肺素衍生物ΔA146Ply主要通过甘露糖受体介导的自噬抑制抑制三阴性乳腺癌转移。
解毒溶气素衍生物ΔA146Ply已被本课题组证实具有直接抗三阴性乳腺癌的作用,但其工作模式尚不清楚。在本研究中,我们重点研究了其抑制三阴性乳腺癌转移的能力。我们发现ΔA146Ply通过激活甘露糖受体和toll样受体4抑制三阴性乳腺癌细胞的迁移和侵袭。它们的激活触发了雷帕霉素信号的哺乳动物靶点的激活,从而导致自噬、转化生长因子-β1和上皮-间质转化抑制。此外,阿霉素和ΔA146Ply联合使用可显著抑制三阴性乳腺癌的进展,延长荷瘤小鼠的生存期。综上所述,我们的研究为三阴性乳腺癌提供了另一种基于微生物组的甘露糖受体靶向治疗方法,并为甘露糖受体下游信号通路提供了新的理论和实验基础。
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来源期刊
Virulence
Virulence IMMUNOLOGY-MICROBIOLOGY
CiteScore
9.20
自引率
1.90%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.
期刊最新文献
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