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），目前死亡率较高（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，并且没有已知的治疗靶点。癌症研究中的先前研究发现支持蛋白质错误定位是癌症中非常常见的现象的概念（Mustachio等人，2017年）。该项目旨在研究粘附蛋白的错误定位的概念，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;特别是对于预后不良的胶质母细胞瘤（Hanif et al.，2017年）。具体而言，侵袭和迁移是肿瘤发展中发生的关键事件（Martin et al. 2013）。这些过程由几种因素促进，例如细胞动力学和细胞外基质（ECM）（Patel等人，2018年）。ECM是人细胞的结构支架，因为它决定了它们的结构并提供支持（Theocharis等人，2016).重要的是，ECM通过从细胞表面受体转导至ECM的信号介导几种细胞功能，例如迁移和分化（Theocharis等人，（Byron and Frame，2016）。重要的是，在先前的研究中，发现在许多癌症中发现了受体酪氨酸激酶运输（Schoenherr et al.，2018年）。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。叶，桑德斯A. J.，莱恩·J江湾W.，（2013）“癌症侵袭和转移：分子和细胞的观点”，居里夫人生物科学数据库。可从：https://www.ncbi.nlm.nih.gov/books/NBK164700/ [访问日期：2019年9月25日] Alphande'ry E.（2018），“胶质母细胞瘤治疗：最近工业发展的帐户”，前线药理学，9，pp.879，DOI：doi：10.3389/fphar.2018.00879 Theocharis A.D.，Skandalis S.S.，Gialeli C Karamanos N.K.，（2016），“细胞外基质结构”，高级药物递送评论。《明史》，第97页。4-27.吉里杰什湾放大图片作者：Haseeb Zubair，Mohammad A.作者：Sanjeev K.放大图片作者：Srivastava，Aamir Ahmad，玛丽C. Patton，Seema Singh，Moh'd Khushman，Ajay P. Singh（2018），“外泌体：肿瘤转移的关键支持者”，外泌体在癌症中的诊断和治疗应用，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），“多形性胶质母细胞瘤：通过临床表现和治疗回顾其流行病学和发病机制”，亚太癌症预防杂志：APJCP，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