MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer

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.

Integrative Analysis of Membrane Proteome and MicroRNA Reveals Novel Lung Cancer Metastasis Biomarkers

“…Membrane proteins as well as extra-cellular matrix (ECM) molecules, cell adhesion molecules and adhesion receptors form into functional complex units and maintain cell–cell adhesions. These complexes, once disassembled, will increase tumor metastasis and invasion ( Gumbiner, 1996 ; Vadakekolathu et al, 2018 ). To further examine the mechanistic role in cancer metastasis of differentially expressed membrane proteins, we performed two-step functional enrichment analysis.…”

miRNA-182 regulated MTSS1 inhibits proliferation and invasion in Glioma Cells

“…MTSS1, as a metastasis suppressor gene, is an actin-binding protein in cytoskeleton function. This protein plays a very important role in cell-cell adhesion 29 . It belongs to the IMD (IRSp53 and MIM domain) family and is a kind of actin-binding scaffold protein involved in the occurrence and metastasis of tumors 30 .…”

UBE2O promotes the proliferation, EMT and stemness properties of breast cancer cells through the UBE2O/AMPKα2/mTORC1-MYC positive feedback loop

“…For the western blot assay, BC cells and tissues were lysed with radioimmunoprecipitation assay (RIPA) (Catalogue Number P0013B, Beyotime, China) buffer containing phenylmethylsulfonyl fluoride (PMSF) (Catalogue Number ST506, Beyotime, China). The lysate was collected, and western blot assays were conducted as previously described 27 . The following antibodies were used for these experiments: UBE2O (15812-1-AP), AMPKα1 (10929-2-AP), AMPKα2 (18167-1-AP), CDH2 (22018-1-AP), CD44 (15675-1-AP), ABCG2 (27286-1-AP), MYC (10828-1-AP) and β-actin (60008-1-Ig), which were purchased from the Proteintech Group.…”