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Lysosomes in glioblastoma: pump up the volume.
Cell Cycle ( IF 4.3 ) Pub Date : 2020-07-29 , DOI: 10.1080/15384101.2020.1796016
Kathryn A Jacobs 1 , Clément Maghe 1 , Julie Gavard 1, 2
Affiliation  

Lysosomes are acidic, dynamic organelles that supervise catabolism, integrate signaling cascades, and tune cellular trafficking. Moreover, the loss of their integrity may jeopardize cell viability. In cancer cells, lysosomes are qualitatively and quantitatively modified for the tumor’s own benefit. For all these reasons, these organelles emerge as appealing intracellular targets to manipulate non-oncogene addiction. This is of particular interest for brain diseases, including neurodegenerative disorders and cancer, in which stem cells are exhausted and transformed, respectively. Recent publications had demonstrated that stem cells displayed disarmed lysosomes in terms of number and functions during aging and oncogenic progression. Likewise, our laboratory identified that the arginine protease MALT1, normally dedicated to the assembly of proper NF-kB activation and processing a number of substrates, arbitrates lysosome biogenesis and mTOR signaling in glioblastoma stem-like cells. Indeed, blocking either the expression or the activity of this enzyme leads to an aberrant increase of lysosomes, alongside of the down-regulation of the mTOR signaling. This surge of lysosomes eradicates glioblastoma stem-like cells. Targeting lysosomes might thus inspire the design of new strategies to face this devastating human cancer. Here, we provide an overview of the functions of the lysosome as well as its role as a cell death initiator, to highlight the potential of lysosomal drugs for glioblastoma therapy.



中文翻译:

胶质母细胞瘤中的溶酶体:增加体积。

溶酶体是酸性的动态细胞器,可监督分解代谢、整合信号级联并调节细胞运输。此外,其完整性的丧失可能危及细胞活力。在癌细胞中,为了肿瘤自身的利益,溶酶体在定性和定量上被修改。由于所有这些原因,这些细胞器成为操纵非致癌基因成瘾的有吸引力的细胞内靶标。这对脑部疾病特别感兴趣,包括神经退行性疾病和癌症,其中干细胞分别被耗尽和转化。最近的出版物表明,在衰老和致癌进展过程中,干细胞在数量和功能方面显示出解除武装的溶酶体。同样,我们的实验室确定精氨酸蛋白酶 MALT1,通常致力于组装适当的 NF-kB 激活和处理许多底物,仲裁溶酶体生物发生和胶质母细胞瘤干细胞样细胞中的 mTOR 信号。事实上,阻断该酶的表达或活性会导致溶酶体异常增加,同时下调 mTOR 信号传导。这种溶酶体的激增根除胶质母细胞瘤干细胞样细胞。因此,靶向溶酶体可能会激发设计新策略以应对这种毁灭性的人类癌症。在这里,我们概述了溶酶体的功能及其作为细胞死亡引发剂的作用,以强调溶酶体药物在胶质母细胞瘤治疗中的潜力。阻断该酶的表达或活性会导致溶酶体异常增加,同时下调 mTOR 信号传导。这种溶酶体的激增根除胶质母细胞瘤干细胞样细胞。因此,靶向溶酶体可能会激发设计新策略以应对这种毁灭性的人类癌症。在这里,我们概述了溶酶体的功能及其作为细胞死亡引发剂的作用,以强调溶酶体药物在胶质母细胞瘤治疗中的潜力。阻断该酶的表达或活性会导致溶酶体异常增加,同时下调 mTOR 信号。这种溶酶体的激增根除胶质母细胞瘤干细胞样细胞。因此,靶向溶酶体可能会激发设计新策略以应对这种毁灭性的人类癌症。在这里,我们概述了溶酶体的功能及其作为细胞死亡引发剂的作用,以强调溶酶体药物在胶质母细胞瘤治疗中的潜力。

更新日期:2020-09-08
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