GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity.
GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity.
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DOI：
10.1038/s43018-023-00556-5
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发表时间：
2023-05
期刊：
影响因子：
22.7
通讯作者：
Lathia, Justin D. D.
中科院分区：
文献类型：
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作者：
Watson, Dionysios C. C.;Bayik, Defne;Storevik, Simon;Moreino, Shannon Sherwin;Sprowls, Samuel A. A.;Han, Jianhua;Augustsson, Mina Thue;Lauko, Adam;Sravya, Palavalasa;Rosland, Gro Vatne;Troike, Katie;Tronstad, Karl Johan;Wang, Sabrina;Sarnow, Katharina;Kay, Kristen;Lunavat, Taral R.;Silver, Daniel J.;Dayal, Sahil;Joseph, Justin Vareecal;Mulkearns-Hubert, Erin;Ystaas, Lars Andreas Romo;Deshpande, Gauravi;Guyon, Joris;Zhou, Yadi;Magaut, Capucine R.;Seder, Juliana;Neises, Laura;Williford, Sarah E.;Meiser, Johannes;Scott, Andrew J. J.;Sajjakulnukit, Peter;Mears, Jason A. A.;Bjerkvig, Rolf;Chakraborty, Abhishek;Daubon, Thomas;Cheng, Feixiong;Lyssiotis, Costas A. A.;Wahl, Daniel R. R.;Hjelmeland, Anita B. B.;Hossain, Jubayer A. A.;Miletic, Hrvoje;Lathia, Justin D. D.
完整的线粒体在异种细胞类型之间的转移已经在包括癌症在内的各种环境中得到证实。然而，线粒体转移对肿瘤生物学的功能影响还知之甚少。在这里，我们发现线粒体转移是胶质母细胞瘤(GBM)的普遍现象，胶质母细胞瘤是最常见和恶性的原发脑肿瘤。我们发现从星形胶质细胞水平转移线粒体是增强基底膜肿瘤发生的机制。这种转移依赖于GBM细胞和星形胶质细胞之间形成网络的细胞间连接，生长相关蛋白43(GAP43)促进了这种连接，生长相关蛋白43参与了神经元轴突再生和星形胶质细胞的反应。星形胶质细胞线粒体的获得推动了线粒体呼吸的增加和与增殖和致癌相关的代谢途径的上调。在功能上，星形胶质细胞线粒体的摄取促进细胞周期进入增殖的G2/M期，并增强GBM的自我更新和致瘤性。总而言之，我们的发现揭示了宿主-肿瘤的相互作用，推动了癌细胞的增殖和自我更新，为治疗发展提供了机会。Watson等人。证明星形胶质细胞线粒体可以以GAP43依赖的方式水平转移到胶质母细胞瘤细胞，导致线粒体呼吸和代谢的变化，从而促进增殖和肿瘤生长。
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. Watson et al. demonstrate that astrocyte mitochondria can be horizontally transferred to glioblastoma cells in a GAP43-dependent manner, leading to changes in mitochondrial respiration and metabolism that promote proliferation and tumor growth.
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影响因子：
16.6
作者：
Cheng F;Desai RJ;Handy DE;Wang R;Schneeweiss S;Barabási AL;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
7.3
作者：
Jones W;Bianchi K
通讯作者：
Bianchi K
DOI：
10.1007/978-1-4939-8922-5_2
发表时间：
2019-01-01
期刊：
SUICIDE GENE THERAPY
影响因子：
--
作者：
Hossain, Jubayer A.;Riecken, Kristoffer;Fehse, Boris
通讯作者：
Fehse, Boris
影响因子：
3.5
作者：
Nguyen, Lilly;He, Qin;Meiri, Karina F.
通讯作者：
Meiri, Karina F.
影响因子：
5.6
作者：
Civita, Prospero;Leite, Diana M.;Pilkington, Geoffrey J.
通讯作者：
Pilkington, Geoffrey J.