Journal Article

MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer

Regad, Tarik, Ball, Graham Roy, Di Biase, Anna, Vadakekolathu, Jayakumar, Johnson, Catherine, Al-Juboori, Shaymaa Ismael Kadhim, Schneider, Anne, Buczek, Magdalena Elżbieta, Powe, Desmond George, Pockley, Alan Graham

2018

Overview

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.

• Publisher: Nature Publishing Group UK,Springer Nature B.V
• Subject: 13/51 / 14/105 / 14/63 / 38/44 / 38/61 / 82/1 / 82/80 / 96/63 / Antibodies / Biochemistry / Biomedical and Life Sciences / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cell adhesion & migration / Cell adhesion molecules / Cell Biology / Cell Culture / Cell Movement / ErbB-2 protein / Extracellular matrix / Female / Gene expression / Golgi apparatus / Guanosine triphosphate / Humans / Immunology / Invasiveness / Life Sciences / Membrane proteins / Membrane Proteins - genetics / Membrane Proteins - metabolism / Metastases / Metastasis / Microfilament Proteins - genetics / Microfilament Proteins - metabolism / Neoplasm Invasiveness / Neoplasm Proteins - genetics / Neoplasm Proteins - metabolism / Phenotypes / Protein transport / Protein turnover / Proteins / Rac1 protein / Receptor, ErbB-2 - genetics / Receptor, ErbB-2 - metabolism / Receptors, Estrogen - genetics / Receptors, Estrogen - metabolism / Tumors