Dr Eloise van der Merwe – Knockdown of LRP/LR Impedes Multiple Cancer Hallmarks in Lung Cancer Cells
Dr Eloise van der Merwe
Dr Eloise van der Merwe of the School of Molecular and Cell Biology, University of the Witwatersrand delivered a poster at the ASCB/EMBO Cell Bio 2023 conference in Boston, USA from 2-6 December 2023 as part of the late Prof Stefan Weiss’s CANSA-funded project. Read more…
Download the poster
Abstract:
Knockdown of LRP/LR Impedes Multiple Cancer Hallmarks in Lung Cancer Cells
Lung cancer is currently the leading cause of cancer death worldwide. The 37 kDa/67 kDa laminin receptor (LRP/LR), which is overexpressed in various cancer types, plays a role in several cancer hallmarks. Particularly, LRP/LR plays a role in metastasis, by mediating adhesion and invasion, enhancing angiogenesis, maintaining cell viability, and evading apoptosis. In addition, LRP/LR enhances telomerase activity, enabling replicative immortality. The objective of this study was therefore to investigate the effect of siRNA mediated knockdown of LRP/LR on reducing cell viability, migration potential, telomerase activity as well as inducing apoptosis in A549 lung cancer cells. SWATH-MS proteomic analysis was performed to investigate the effect of LRP/LR knockdown on protein expression. A549 cells exhibited a significant decrease in cell viability, migration potential and telomerase activity, as well as a significant increase in apoptosis after knockdown of LRP/LR. Furthermore, proteomic analysis performed after LRP/LR knockdown revealed upregulation of several proteins involved in the MHC I antigen presentation pathway, indicating the possible re-establishment of immune control over the cells. Not only does this indicate the inhibition of another key cancer hallmark, but also reveals a novel function of LRP/LR in its oncogenic form, as contributing to evasion of immune destruction. Additionally, proteomic analysis highlighted the upregulation of numerous proteins with tumour suppressor functions that are specifically involved in cell cycle modulation and apoptosis, further confirming the activation of apoptosis, as well as suggesting the induction of cell growth repressors with consequent cell cycle arrest. These observations indicate that LRP/LR is crucial for the maintenance of lung cancer cells, and we therefore suggest that targeting LRP/LR may have therapeutic potential for inhibiting several cancer hallmarks.
