Quantitative proteomic analysis of dysregulated adhesion protein localisation in patient-derived cancer cells

胶质母细胞瘤是一种起源于胶质细胞的肿瘤（星形细胞瘤），目前死亡率很高（Alphande'ry 2018）。尽管癌症研究取得了进展，但唯一可用的治疗方法是手术切除和化疗的结合，目前还没有已知的治疗靶点。先前的癌症研究结果支持蛋白质错定位是癌症中非常常见的现象（Mustachio et al., 2017）。该项目旨在研究粘附蛋白错定位的概念，并了解它们在胶质母细胞瘤中的相互作用；这将有助于确定靶点，并可能提出新的治疗策略。为了实现这一目标，在癌症研究中更好地了解导致肿瘤发展的分子功能至关重要；尤其是胶质母细胞瘤，因为其预后较差（Hanif et al., 2017）。具体来说，侵袭和迁移是肿瘤发展过程中的关键事件（Martin et al. 2013）。这些过程受到细胞动力学和细胞外基质（ECM）等几个因素的促进（Patel等人，2018）。ECM是人体细胞的结构支架，因为它决定了细胞的结构并提供支持（Theocharis et al., 2016）。重要的是，ECM通过从细胞表面受体转导到ECM的信号介导多种细胞功能，如迁移和分化（Theocharis等人，2016），（Byron和Frame， 2016）。重要的是，在之前的研究中，发现在许多癌症中发现了受体酪氨酸激酶的贩运（Schoenherr等人，2018）。因此，ECM的失调导致癌症，该项目的主要目的是鉴定脑癌的亚细胞蛋白质组。（2013）“肿瘤侵袭与转移：分子与细胞的视角”，《Madame Curie Bioscience》数据库。Alphande'ry E.(2018)，“胶质母细胞瘤治疗：近期工业发展”，《前沿医药》，9,pp.879, DOI: DOI: 10.3389/fphar.2018.00879 Theocharis A.D., Skandalis S.S s., Gialeli C., Karamanos N.K,(2016)，“细胞外基质结构”，先进药物递送评论，97,pp. 4-27。Girijesh K. Patel, Haseeb Zubair, Mohammad A. Khan, Sanjeev K. Srivastava, Aamir Ahmad, Mary C. Patton, Seema Singh, Moh'd Khushman, Ajay P. Singh(2018)，“外逸体：肿瘤转移的关键支持者”，癌症外逸体的诊断和治疗应用，学术出版社，261-283,DOI: https://doi.org/10.1016/B978-0-12- 812774-2.00015-8Hanif， F., Muzaffar， K., Perveen， K., Malhi, s.m ., & Simjee， S.(2017)，“多形性胶质母细胞瘤：从临床表现和治疗的角度分析其流行病学和发病机制[j] .中华肿瘤防治杂志，18(1),pp. 3-9。DOI: 10.22034/APJCP .2017.18.1.3 Schoenherr， C., Frame， M., & Byron， A.（2018）“粘附和生长因子受体及其效应激酶的贩运”。细胞与发育生物学年度评论，34(1),pp. 29-58, DOI: 10.1146/annurev-cellbio-100617-062559

Glioblastoma is a type of tumour (astrocytomas) that originates from glial cells and currently has high mortality rate (Alphande'ry 2018). Despite advances in cancer research, the only available treatment is a combination of surgical removal and chemotherapy and there are not known therapeutic targets. Previous research findings in cancer research support the concept that protein mislocalisation is a very frequent phenomenon in cancer (Mustachio et al., 2017). This project is designed to study the concept of mislocalisation of adhesion proteins and understand their interaction in glioblastoma; this would help determine targets and potentially suggest novel therapeutic strategies.In order to achieve this, it is critical to gain a better understanding of the molecular functions that lead to tumour development in cancer research; especially for glioblastoma due to its poor prognosis (Hanif et al., 2017). Specifically, invasion and migration are key events happening in tumour development (Martin et al. 2013). These processes are facilitated by several factors such as cellular dynamics and Extracellular Matrix (ECM) (Patel et al., 2018). ECM is a structural scaffold of human cells because it determines their structure and offers support (Theocharis et al., 2016).Importantly the ECM mediates several cellular functions such as migration and differentiation through signals that are transduced to the ECM from cell surface receptors (Theocharis et al., 2016), (Byron and Frame, 2016). Importantly in previous studies, it was found that Receptor Tyrosine Kinases trafficking has been found in many cancers (Schoenherr et al., 2018). Hence, dysregulation of the ECM leads to cancer and the main purpose of the project is to identify the subcellular proteomes of brain cancer.BibliographyMartin T.A., Ye L., Sanders A.J., Lane J., Jiang G. W., (2013) 'Cancer Invasion and Metastasis: Molecular and Cellular Perspective', Madame Curie Bioscience Database. Available from: https://www.ncbi.nlm.nih.gov/books/NBK164700/ [Accessed on: 25/09/2019] Alphande'ry E. (2018), 'Glioblastoma Treatments: An Account of Recent Industrial Developments', Front Pharmacol,9, pp.879, DOI: doi:10.3389/fphar.2018.00879 Theocharis A.D., Skandalis S.S., Gialeli C., Karamanos N.K., (2016), 'Extracellular matrix structure', Advanced Drug Delivery Reviews. 97, pp. 4-27.Girijesh K. Patel, Haseeb Zubair, Mohammad A. Khan, Sanjeev K. Srivastava, Aamir Ahmad, Mary C. Patton, Seema Singh, Moh'd Khushman, Ajay P. Singh (2018),'Exosomes: Key Supporters of Tumor Metastasis', Diagnostic and Therapeutic Applications of Exosomes in Cancer,Academic Press, pp. 261-283, DOI: https://doi.org/10.1016/B978-0-12- 812774-2.00015-8Hanif, F., Muzaffar, K., Perveen, K., Malhi, S. M., & Simjee, S. (2017), 'Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation andTreatment', Asian Pacific journal of cancer prevention: APJCP, 18(1), pp. 3-9. DOI: 10.22034/APJCP .2017.18.1.3 Schoenherr, C., Frame, M., & Byron, A. (2018) 'Trafficking of Adhesion and Growth Factor Receptors and Their Effector Kinases'. Annual Review of Cell And Developmental Biology, 34(1), pp. 29-58, DOI: 10.1146/annurev-cellbio-100617-062559