Proteomics Identifies Osteomodulin as a Promoter of Breast Cancer Bone Metastasis via CDK1 Activation

Sara Cabral; Joseph Parsons; Hannah Harrison; Thomas Kedward; Paul Fullwood; Katherine Spence; Diane V.  Lefley; Danielle Barden; Jennifer Ferguson; Joanne Watson; Kalliopi P Tsafou; Caron Behan; Mark J. Dunning; Nisha Ali; Balázs Győrffy; Janet Brown; Michael P. Smith; Penelope D Ottewell; Ciara O’Brien; Chiara Francavilla; Robert B. Clarke

doi:10.1101/2023.11.03.565489

Proteomics Identifies Osteomodulin as a Promoter of Breast Cancer Bone Metastasis via CDK1 Activation

Sara Cabral
, Joseph Parsons
, Hannah Harrison
, Thomas Kedward
, Paul Fullwood
, Katherine Spence
, Diane V. Lefley
, Danielle Barden
, Jennifer Ferguson
, Joanne Watson
, Kalliopi P Tsafou
, Caron Behan
, Mark J. Dunning
, Nisha Ali
, Balázs Győrffy
, Janet Brown
, Michael P. Smith
, Penelope D Ottewell
, Ciara O’Brien
, Chiara Francavilla

Robert B. Clarke

Research output: Preprint/Working paper › Preprint

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.

Original language	English
Publisher	bioRxiv
Pages	1-63
Number of pages	63
DOIs	https://doi.org/10.1101/2023.11.03.565489
Publication status	Published - 28 Jul 2025

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Cabral, S., Parsons, J., Harrison, H., Kedward, T., Fullwood, P., Spence, K., Lefley, D. V., Barden, D., Ferguson, J., Watson, J., Tsafou, K. P., Behan, C., Dunning, M. J., Ali, N., Győrffy, B., Brown, J., Smith, M. P., Ottewell, P. D., O’Brien, C., ... Clarke, R. B. (2025). Proteomics Identifies Osteomodulin as a Promoter of Breast Cancer Bone Metastasis via CDK1 Activation. (pp. 1-63). bioRxiv. https://doi.org/10.1101/2023.11.03.565489

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title = "Proteomics Identifies Osteomodulin as a Promoter of Breast Cancer Bone Metastasis via CDK1 Activation",

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.",

author = "Sara Cabral and Joseph Parsons and Hannah Harrison and Thomas Kedward and Paul Fullwood and Katherine Spence and Lefley, \{Diane V.\} and Danielle Barden and Jennifer Ferguson and Joanne Watson and Tsafou, \{Kalliopi P\} and Caron Behan and Dunning, \{Mark J.\} and Nisha Ali and Bal{\'a}zs Gy{\H o}rffy and Janet Brown and Smith, \{Michael P.\} and Ottewell, \{Penelope D\} and Ciara O{\textquoteright}Brien and Chiara Francavilla and Clarke, \{Robert B.\}",

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doi = "10.1101/2023.11.03.565489",

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Cabral, S, Parsons, J, Harrison, H, Kedward, T, Fullwood, P, Spence, K, Lefley, DV, Barden, D, Ferguson, J, Watson, J, Tsafou, KP, Behan, C, Dunning, MJ, Ali, N, Győrffy, B, Brown, J, Smith, MP, Ottewell, PD, O’Brien, C, Francavilla, C & Clarke, RB 2025 'Proteomics Identifies Osteomodulin as a Promoter of Breast Cancer Bone Metastasis via CDK1 Activation' bioRxiv, pp. 1-63. https://doi.org/10.1101/2023.11.03.565489

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AU - Spence, Katherine

AU - Lefley, Diane V.

AU - Barden, Danielle

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AU - Watson, Joanne

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AU - Behan, Caron

AU - Dunning, Mark J.

AU - Ali, Nisha

AU - Győrffy, Balázs

AU - Brown, Janet

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AB - 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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BT - Proteomics Identifies Osteomodulin as a Promoter of Breast Cancer Bone Metastasis via CDK1 Activation

PB - bioRxiv

ER -

Proteomics Identifies Osteomodulin as a Promoter of Breast Cancer Bone Metastasis via CDK1 Activation

Abstract

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