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oai:figshare.com:article/32805359 2026-10-01T16:16:14Z portal_1172 item_type_8 month_year_10_2026

Bioinformatics-driven insights into the role of cathepsins in tumour biology Samantha A. Gallaher (24292655) PUREID: 673799309 cancer DNA damage repair DNA damage response DNA damage proteases Cathepsin S Cathepsin V breast cancer bioinformatics RNA-sequencing <div>Cysteine cathepsins are proteolytic enzymes implicated in cancer progression through their involvement in tumour growth, extracellular matrix (ECM) remodelling, and modulation of the tumour microenvironment (TME). This thesis examines the molecular roles of two cysteine cathepsins, cathepsin S (CTSS) and cathepsin V (CTSV), with a focus on their relevance to breast cancer biology and disease aggressiveness.</div><div>Using bioinformatic approaches, CTSS expression was examined across a range of malignancies, where elevated expression was associated with features of aggressive disease. Further analyses identified links between CTSS expression patterns and cellular responses to genomic stress. Complementary <i>in vitro </i>experiments demonstrated that genotoxic stress conditions can modulate CTSS expression in breast cancer cell models and influence invasive cellular behaviours, supporting a functional role for CTSS in tumour progression. These findings suggest that CTSS activity is responsive to perturbations in genome maintenance pathways, although the precise regulatory mechanisms require further investigation.</div><div>This thesis also explores the role of CTSV in breast cancer. Transcriptomic analyses indicated associations between CTSV expression and pathways involved in cell proliferation and phenotypic plasticity. Functional studies revealed that modulation of CTSV expression produces context-dependent effects across breast cancer subtypes, highlighting heterogeneity in cathepsin-mediated signalling and tumour behaviour.</div><div>Overall, this work advances understanding of the involvement of CTSS and CTSV in breast cancer and underscores the complexity of protease regulation in oncogenic contexts. The findings support the potential relevance of cysteine cathepsins as biomarkers and therapeutic targets, while providing a platform for future studies aimed at clarifying their clinical significance and mechanistic roles in cancer progression.</div><br><i>Thesis embargoed until 31st July 2031</i> 2026-10-01T16:16:14Z Text Thesis 10.17034/32805359.v1 https://figshare.com/articles/thesis/Bioinformatics-driven_insights_into_the_role_of_cathepsins_in_tumour_biology/32805359 All Rights Reserved Open Access after 2031-07-31