Proteostatic regulation of glioblastoma stemness

胶质母细胞瘤是成人中最具侵袭性的脑癌类型。该病无法治愈，大多数患者在诊断后15-18个月内死亡，即使接受治疗。开发针对胶质母细胞瘤的有效疗法非常困难，因为这些癌症是由不同癌细胞的非常多样化的混合物组成的。我们发现，一种比这种癌症的其他细胞更具侵略性的胶质母细胞瘤细胞也比侵略性较低的胶质母细胞瘤细胞含有更多的蛋白质。我们认为这使得更具攻击性的胶质母细胞瘤细胞生长得更快，这有助于这些细胞更具攻击性，并在治疗后重新生长成新的肿瘤。我们的项目将研究更具攻击性和攻击性较低的胶质母细胞瘤细胞之间的蛋白质差异，以通过阻止更具攻击性的细胞生长来寻找治疗胶质母细胞瘤的新方法。我们希望了解蛋白质的生产是如何进行的每一种胶质母细胞瘤细胞类型，我们将联合收割机不同的方式调查胶质母细胞瘤细胞内的蛋白质。这将使我们不仅能够研究蛋白质的类型，而且还可以研究它们如何相互作用以及它们如何被分解。作为我们项目的一部分，我们将研究蛋白质HECTD 1，因为它控制着制造蛋白质的工厂，称为核糖体。我们将测试HECTD 1是否有助于更具攻击性的胶质母细胞瘤细胞产生更多的蛋白质，从而帮助胶质母细胞瘤在治疗后重新生长。这可能有助于找到治疗胶质母细胞瘤的新方法。最后，我们正在使用一种新型显微镜来测量胶质母细胞瘤细胞类型内的蛋白质量，这是令人兴奋的，因为这项技术有可能很容易地识别更具侵略性的胶质母细胞瘤细胞，灵敏度更高，速度比以往任何时候都快。我们将在人类患者材料中测试这一点，以评估其诊断/预后价值。这项新技术可以帮助其他科学家和临床医生在未来更容易识别和研究更具侵略性的癌细胞。

Glioblastoma is the most aggressive type of brain cancer in adults. There is no cure, and most patients die within 15-18 months after diagnosis, even with treatment. Developing effective therapies against glioblastoma is very difficult, because these cancers are made up of a very diverse mixture of different cancer cells. We have found that a type of glioblastoma cells that is more aggressive than other cells from this cancer also contains more proteins than less aggressive glioblastoma cells. We think this allows more aggressive glioblastoma cells to grow quicker which helps these cells to be more aggressive and regrow into new tumours after treatment. Our project will investigate differences in proteins between more aggressive and less aggressive glioblastoma cells to find new ways for treating glioblastoma by stopping more aggressive cells from growing. We want to understand how protein production is conducted in each glioblastoma cell type, and we will combine different ways of investigating proteins inside glioblastoma cells. This will allow us to study not only the type of proteins being made, but also how they interact with one another and how they are broken down. As part of our project, we will investigate the protein HECTD1 since it controls the factory which makes proteins, called the ribosome. We will test whether HECTD1 helps more aggressive glioblastoma cells to make more protein and therefore helps glioblastomas to grow back after therapy. This may help find new ways of treating glioblastoma. Finally, we are using a new type of microscope for measuring protein amounts inside glioblastoma cell types and this is exciting because this technology has the potential to readily identify more aggressive glioblastoma cells, with increased sensitivity and quicker than ever before. We will test this in human patient material to evaluate its diagnostic/prognostic value. This new technology could help other scientists and clinicians in the future by making it easier to identify and study more aggressive cancer cells.