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

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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