Next Article in Journal
Specificity of Escherichia coli Heat-Labile Enterotoxin Investigated by Single-Site Mutagenesis and Crystallography
Next Article in Special Issue
The Impact of Tumor Heterogeneity on Diagnostics and Novel Therapeutic Strategies in Multiple Myeloma
Previous Article in Journal
Insertion Hot Spots of DIRS1 Retrotransposon and Chromosomal Diversifications among the Antarctic Teleosts Nototheniidae
Previous Article in Special Issue
Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update
Open AccessArticle

TRAF6 Silencing Attenuates Multiple Myeloma Cell Adhesion to Bone Marrow Stromal Cells

Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7BL, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 702; https://doi.org/10.3390/ijms20030702
Received: 6 December 2018 / Revised: 30 January 2019 / Accepted: 30 January 2019 / Published: 6 February 2019
(This article belongs to the Special Issue Novel Therapeutic Strategies in Multiple Myeloma)
The bone marrow (BM) microenvironment plays an important role in supporting proliferation, survival and drug resistance of Multiple Myeloma (MM) cells. MM cells adhere to bone marrow stromal cells leading to the activation of tumour-promoting signaling pathways. Activation of the NFκB pathway, in particular, is central to the pathogenesis of MM. Tumour necrosis factor receptor-associated factor 6 (TRAF6) is a key mediator of NFκB activation and has previously been highlighted as a potential therapeutic target in MM. Here, we demonstrate that adherence of MM cell lines to stromal cells results in a reciprocal increase in TRAF6 expression. Knockdown of TRAF6 expression attenuates the ability of MM cells to bind to stromal cells and this is associated with a decrease in NFκB-induced expression of the adhesion molecules ICAM1 and VCAM1. Finally, we show that knockdown of TRAF6 sensitizes MM cells to treatment with bortezomib when co-cultured with stromal cells. Inhibiting TRAF6 represents a promising strategy to target MM cells in the BM microenvironment. View Full-Text
Keywords: Multiple Myeloma; TRAF6; BMSCs Multiple Myeloma; TRAF6; BMSCs
Show Figures

Graphical abstract

MDPI and ACS Style

Morgan, J.J.; McAvera, R.M.; Crawford, L.J. TRAF6 Silencing Attenuates Multiple Myeloma Cell Adhesion to Bone Marrow Stromal Cells. Int. J. Mol. Sci. 2019, 20, 702.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop