MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer

Vadakekolathu, J., Al-Juboori, S.I.K., Johnson, C., Schneider, A., Buczek, M.E., Di Biase, A., Pockley, A.G. ORCID: 0000-0001-9593-6431, Ball, G.R. ORCID: 0000-0001-5828-7129, Powe, D.G. and Regad, T. ORCID: 0000-0003-4028-6368, 2018. MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer. Cell Death & Disease, 9: 344. ISSN 2041-4889

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Abstract

Cell–cell adhesions constitute the structural “glue” that retains cells together and contributes to tissue organisation and physiological function. The integrity of these structures is regulated by extracellular and intracellular signals and pathways that act on the functional units of cell adhesion such as the cell adhesion molecules/adhesion receptors, the extracellular matrix (ECM) proteins and the cytoplasmic plaque/peripheral membrane proteins. In advanced cancer, these regulatory pathways are dysregulated and lead to cell–cell adhesion disassembly, increased invasion and metastasis. The Metastasis suppressor protein 1 (MTSS1) plays a key role in the maintenance of cell–cell adhesions and its loss correlates with tumour progression in a variety of cancers. However, the mechanisms that regulate its function are not well-known. Using a system biology approach, we unravelled potential interacting partners of MTSS1. We found that the secretory carrier-associated membrane protein 1 (SCAMP1), a molecule involved in post-Golgi recycling pathways and in endosome cell membrane recycling, enhances Mtss1 anti-invasive function in HER2+/ER−/PR− breast cancer, by promoting its protein trafficking leading to elevated levels of RAC1-GTP and increased cell–cell adhesions. This was clinically tested in HER2 breast cancer tissue and shown that loss of MTSS1 and SCAMP1 correlates with reduced disease-specific survival. In summary, we provide evidence of the cooperative roles of MTSS1 and SCAMP1 in preventing HER2+/ER−/PR− breast cancer invasion and we show that the loss of Mtss1 and Scamp1 results in a more aggressive cancer cell phenotype.

Item Type: Journal article
Publication Title: Cell Death & Disease
Creators: Vadakekolathu, J., Al-Juboori, S.I.K., Johnson, C., Schneider, A., Buczek, M.E., Di Biase, A., Pockley, A.G., Ball, G.R., Powe, D.G. and Regad, T.
Publisher: Springer Nature on behalf of the Cell Death Differentiation Association
Date: 1 March 2018
Volume: 9
ISSN: 2041-4889
Identifiers:
NumberType
10.1038/s41419-018-0364-9DOI
364Publisher Item Identifier
Rights: © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Divisions: Schools > School of Science and Technology
Depositing User: Jill Tomkinson
Date Added: 06 Mar 2018 09:13
Last Modified: 06 Mar 2018 09:13
URI: http://irep.ntu.ac.uk/id/eprint/32851

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