Next Article in Journal
Metabolic Regulation of Hypoxia-Inducible Transcription Factors: The Role of Small Molecule Metabolites and Iron
Next Article in Special Issue
Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
Previous Article in Journal / Special Issue
The Crosstalk of Endoplasmic Reticulum (ER) Stress Pathways with NF-κB: Complex Mechanisms Relevant for Cancer, Inflammation and Infection
Article Menu
Issue 2 (June) cover image

Export Article

Open AccessReview
Biomedicines 2018, 6(2), 59; https://doi.org/10.3390/biomedicines6020059

The NF-κB Activating Pathways in Multiple Myeloma

Systems Immunology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India
Present Address: La Jolla Institute of Allergy and Immunology, La Jolla, CA 92037, USA.
*
Author to whom correspondence should be addressed.
Received: 12 March 2018 / Revised: 14 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)
View Full-Text   |   Download PDF [1059 KB, uploaded 16 May 2018]   |  

Abstract

Multiple myeloma(MM), an incurable plasma cell cancer, represents the second most prevalent hematological malignancy. Deregulated activity of the nuclear factor kappaB (NF-κB) family of transcription factors has been implicated in the pathogenesis of multiple myeloma. Tumor microenvironment-derived cytokines and cancer-associated genetic mutations signal through the canonical as well as the non-canonical arms to activate the NF-κB system in myeloma cells. In fact, frequent engagement of both the NF-κB pathways constitutes a distinguishing characteristic of myeloma. In turn, NF-κB signaling promotes proliferation, survival and drug-resistance of myeloma cells. In this review article, we catalog NF-κB activating genetic mutations and microenvironmental cues associated with multiple myeloma. We then describe how the individual canonical and non-canonical pathways transduce signals and contribute towards NF-κB -driven gene-expressions in healthy and malignant cells. Furthermore, we discuss signaling crosstalk between concomitantly triggered NF-κB pathways, and its plausible implication for anomalous NF-κB activation and NF-κB driven pro-survival gene-expressions in multiple myeloma. Finally, we propose that mechanistic understanding of NF-κB deregulations may provide for improved therapeutic and prognostic tools in multiple myeloma. View Full-Text
Keywords: NF-κB; multiple myeloma; canonical; non-canonical; mutations; microenvironment; cytokines; crosstalk; gene-expressions NF-κB; multiple myeloma; canonical; non-canonical; mutations; microenvironment; cytokines; crosstalk; gene-expressions
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Roy, P.; Sarkar, U.A.; Basak, S. The NF-κB Activating Pathways in Multiple Myeloma. Biomedicines 2018, 6, 59.

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.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomedicines EISSN 2227-9059 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top