Characterisation of the protease Cathepsin S as a novel therapeutic target in triple-negative breast cancer

Cathepsin S (CatS) is a lysosomal protease, overexpressed in multiple cancer types. Preliminary studies revealed in TNBC cells with BRCA1 dysfunction, CatS expression was elevated.

It was hypothesised that BRCA1 dysfunction in TNBC contributed to increased CatS expression, and this promoted TNBC invasion and metastasis. 4T1 shBRCA1, shCatS, and CatS overexpressing cell lines were developed. Increased CatS expression in the shBRCA1 and CatS overexpressing cells increased invasion in vitro. shCatS cells or CatS inhibitor treatment reduced this invasiveness, showing that CatS contributed to driving invasion in vitro. 4T1 shBRCA1 and 4T1 shCatS cells were used in syngeneic mammary implant in vivo models to study the impact on primary tumour growth and metastasis.