Uncovering a novel regulator of triple negative breast cancer cell behaviour

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited targeted treatment options. Previous work identified Nogo-66 receptor-related protein 3 (NgR3), a receptor primarily known for its role in the nervous system, as a potential target of interest in TNBC. However, almost nothing was known about what NgR3 was doing in these cancer cells.

This PhD investigated whether NgR3 is expressed and functionally relevant in TNBC, what molecular pathways are altered when NgR3 is disrupted and whether different approaches to targeting NgR3 produce different biological effects. NgR3 protein was detected across multiple TNBC cell lines. In MDA-MB-231 cells, antibody-mediated targeting of NgR3 reduced proliferation, migration and invasion, while increasing sensitivity to TNF-α-induced apoptotic stress. Transcriptomic analysis also revealed that antibody targeting and siRNA-mediated NgR3 depletion produced distinct pathway-level responses, suggesting that different methods of disrupting NgR3 may affect TNBC cells in different ways.

Together, these findings identify NgR3 as a previously uncharacterised component of TNBC biology and provide a foundation for understanding how this receptor may influence aggressive tumour-associated behaviours.