文章目录

星形胶质细胞gap43依赖性线粒体转移增强胶质母细胞瘤的致瘤性

原文发布日期：2023-05-11

英文摘要：

摘要翻译：

原文链接：

文章：

星形胶质细胞gap43依赖性线粒体转移增强胶质母细胞瘤的致瘤性

GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity

原文发布日期：2023-05-11

英文摘要：

The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications of mitochondria transfer on tumor biology are poorly understood. Here we show that mitochondria transfer is a prevalent phenomenon in glioblastoma (GBM), the most frequent and malignant primary brain tumor. We identified horizontal mitochondria transfer from astrocytes as a mechanism that enhances tumorigenesis in GBM. This transfer is dependent on network-forming intercellular connections between GBM cells and astrocytes, which are facilitated by growth-associated protein 43 (GAP43), a protein involved in neuron axon regeneration and astrocyte reactivity. The acquisition of astrocyte mitochondria drives an increase in mitochondrial respiration and upregulation of metabolic pathways linked to proliferation and tumorigenicity. Functionally, uptake of astrocyte mitochondria promotes cell cycle progression to proliferative G2/M phases and enhances self-renewal and tumorigenicity of GBM. Collectively, our findings reveal a host–tumor interaction that drives proliferation and self-renewal of cancer cells, providing opportunities for therapeutic development.

摘要翻译：

在多种情况下,包括癌症中,不同细胞类型之间的完整线粒体转移已得到证实。然而,线粒体迁移对肿瘤生物学的功能性影响尚不完全理解。我们在其中表明,线粒体迁移是胶质母细胞瘤(glioblastoma,GBM)中最常见的现象之一。我们发现,星形细胞向胶质母细胞迁移的线粒体可作为促进胶质母细胞瘤形成的机制。这种转移依赖于胶质母细胞与星形细胞之间形成网络连接的过程,这些连接由生长相关蛋白43(GAP43)促进,GAP43参与神经纤维再生和星形细胞活性。通过星形细胞的线粒体获得细胞导致线粒体呼吸增加以及激活与增殖和肿瘤性相关的代谢途径。在功能上,星形细胞线粒体的摄取促进了胶质母细胞向增殖G2/M期的过渡并增强了其自更新和肿瘤性。总体而言,我们发现了一个主机-肿瘤相互作用,推动癌细胞的增殖和自我更新,这为治疗提供了可能性。