文章：

磷酸化蛋白质组学分析揭示mTOR信号通路在维持巨噬细胞吞噬癌细胞中的作用

Phosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells

原文发布日期：19 December 2024

DOI: 10.3390/cancers16244238

类型: Article

开放获取: 是

英文摘要：

Background: Macrophage-mediated cancer cell phagocytosis has demonstrated considerable therapeutic potential. While the initiation of phagocytosis, facilitated by interactions between cancer cell surface signals and macrophage receptors, has been characterized, the mechanisms underlying its sustentation and attenuation post-initiation remain poorly understood.Methods: Through comprehensive phosphoproteomic profiling, we interrogated the temporal evolution of the phosphorylation profiles within macrophages during cancer cell phagocytosis.Results: Our findings reveal that activation of the mTOR pathway occurs following the initiation of phagocytosis and is crucial in sustaining phagocytosis of cancer cells. mTOR inhibition impaired the phagocytic capacity, but not affinity, of the macrophages toward the cancer cells by delaying phagosome maturation and impeding the transition between non-phagocytic and phagocytic states of macrophages.Conclusions: Our findings delineate the intricate landscape of macrophage phagocytosis and highlight the pivotal role of the mTOR pathway in mediating this process, offering valuable mechanistic insights for therapeutic interventions.

摘要翻译： 

背景：巨噬细胞介导的癌细胞吞噬作用已显示出显著的治疗潜力。尽管由癌细胞表面信号与巨噬细胞受体相互作用启动的吞噬过程已有研究，但其启动后的持续与衰减机制仍不明确。 方法：通过全面的磷酸化蛋白质组学分析，我们探究了巨噬细胞在吞噬癌细胞过程中磷酸化谱的时序演变。 结果：研究发现，吞噬作用启动后mTOR通路被激活，这对维持癌细胞吞噬至关重要。抑制mTOR通路会延缓吞噬体成熟，阻碍巨噬细胞从非吞噬状态向吞噬状态的转变，从而削弱巨噬细胞对癌细胞的吞噬能力，但不影响其亲和力。 结论：本研究揭示了巨噬细胞吞噬作用的复杂调控机制，并阐明了mTOR通路在该过程中的关键作用，为治疗干预提供了重要的机制性见解。

原文链接：

Phosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells