Proteomics of Patient-derived Breast Tumours Identifies a Pro-migratory Osteomodulin-Cyclin Dependent Kinase 1 Axis which Drives Bone Metastasis

Parsons, J.; Harrison, H.; Kedward, T.; Fullwood, P.; Cabral, S.; Spence, K.; Barden, D.; Haworth, J.; Watson, J.; Tsafou, K.; Behan, C.; Ali, N.; Smith, M.; O'Brien, C.; Clarke, R.; Francavilla, C.

doi:10.1101/2023.11.03.565489

bioRxiv · 10.1101/2023.11.03.565489

Proteomics of Patient-derived Breast Tumours Identifies a Pro-migratory Osteomodulin-Cyclin Dependent Kinase 1 Axis which Drives Bone Metastasis

Parsons, J.·Harrison, H.·Kedward, T.·Fullwood, P.·Cabral, S.·Spence, K.·Barden, D.·Haworth, J.·Watson, J.·Tsafou, K.·Behan, C.·Ali, N.·Smith, M.·O'Brien, C.·Clarke, R.·Francavilla, C.

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Abstract

Metastasis to different organs remains the main cause of mortality in breast cancer. Molecular predictors of metastasis are limited as well as therapeutic options. Here, we conducted quantitative proteomics and phosphoproteomics analysis of patient-derived tumours, identifying osteomodulin (OMD) as a dysregulated protein and associated with bone metastases. Cancer-associated fibroblasts secrete OMD which increases breast cancer migration in vitro and promotes the formation of bone metastases in vivo. Downstream of OMD, phosphoproteomics identified the activation of cyclin-dependent kinase 1 (CDK1). The OMD-CDK1 signalling axis drives a pro-migratory and pro-survival phenotype in vitro and bone metastasis in vivo. Our findings highlight the importance of OMD and CDK1 in breast cancer bone metastasis and proposes an alternative therapeutic avenue for the treatment and the prevention of organ-specific metastases.

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Parsons, J., Harrison, H., Kedward, T., Fullwood, P., Cabral, S., Spence, K., Barden, D., Haworth, J., Watson, J., Tsafou, K., Behan, C., Ali, N., Smith, M., O'Brien, C., Clarke, R., Francavilla, C.. 2023-11-05. Proteomics of Patient-derived Breast Tumours Identifies a Pro-migratory Osteomodulin-Cyclin Dependent Kinase 1 Axis which Drives Bone Metastasis. https://doi.org/10.1101/2023.11.03.565489

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