Investigating the role of sortilin in complex with two tyrosine receptor kinases- EGFR and TrkB, and the crosstalk with the anti-inflammatory pathway

Abstract

Cancer is a disease in which cells within a particular part of the body grow and reproduce uncontrollably. Breast and lung cancer which are used as models within this study are two of the most common malignancies amongst the human population. With over 80% of lung cancer cases being non-small lung cancer; lung cancer is considered being the leading cause of cancer deaths worldwide. Breast cancer however is considered the most frequent malignancy amongst the female population. In this study lung and breast cancer cell lines were used to characterise the effect of sortilin expression because sortilin is a known receptor which is a key regulator in cancer cell development. This study demonstrates that the increased expression levels in the SKMES-1 and MDA-MB-468 cell line appears to decrease cell proliferation, migration and increases cell invasion. In this study a bioinformatic approach was also undertaken to observe the TES complex which involves sortilin, the epidermal growth factor receptor (EGFR) and the Tyrosine kinase receptor B (TrkB). In this study the observation between the two SORT1a variants was observed computationally to determine their differences individually and alongside EGFR and TrkB. The difference between the variants is the change at position 278aa, with KAD transforming to TD, from variant 1 to variant 2. The TES complex has been observed in NSCLC only and has the ability to control both cell migration and the activation of angiogenesis. So, this bioinformatic approach aids in the understanding of how the TES complex is formed. This study also explores small molecule compounds which target the trimeric complex involving p50/p65:IkBa of the activation in the NFkB pathway. These effect of the molecules on cell proliferation and migration are unknown so this study will determine the effects on cancer.

Date of Award	2022
Original language	English