Next Article in Journal
Synthesis of Naphthalene-Based Push-Pull Molecules with a Heteroaromatic Electron Acceptor
Next Article in Special Issue
Antitumor Effect of the Mannich Base(1,3-bis-((3-Hydroxynaphthalen-2-yl)phenylmethyl)urea) on Hepatocellular Carcinoma
Previous Article in Journal
Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo
Previous Article in Special Issue
Alisol F 24 Acetate Enhances Chemosensitivity and Apoptosis of MCF-7/DOX Cells by Inhibiting P-Glycoprotein-Mediated Drug Efflux
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(3), 290; doi:10.3390/molecules21030290

The Role of CD44 and ERM Proteins in Expression and Functionality of P-glycoprotein in Breast Cancer Cells

1
Discipline of Pharmacy, The Graduate School of Health, University of Technology Sydney, Sydney NSW 2007, Australia
2
Proteomics Core Facility, University of Technology Sydney, Sydney NSW 2007, Australia
3
The ithree Institute, University of Technology Sydney, Sydney NSW 2007, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Helena Vasconcelos
Received: 16 December 2015 / Revised: 22 February 2016 / Accepted: 23 February 2016 / Published: 1 March 2016
(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)
View Full-Text   |   Download PDF [2866 KB, uploaded 1 March 2016]   |  

Abstract

Multidrug resistance (MDR) is often attributed to the over-expression of P-glycoprotein (P-gp), which prevents the accumulation of anticancer drugs within cells by virtue of its active drug efflux capacity. We have previously described the intercellular transfer of P-gp via extracellular vesicles (EVs) and proposed the involvement of a unique protein complex in regulating this process. In this paper, we investigate the role of these mediators in the regulation of P-gp functionality and hence the acquisition of MDR following cell to cell transfer. By sequentially silencing the FERM domain-binding proteins, Ezrin, Radixin and Moesin (ERM), as well as CD44, which we also report a selective packaging in breast cancer derived EVs, we have established a role for these proteins, in particular Radixin and CD44, in influencing the P-gp-mediated MDR in whole cells. We also report for the first time the role of ERM proteins in the vesicular transfer of functional P-gp. Specifically, we demonstrate that intercellular membrane insertion is dependent on Ezrin and Moesin, whilst P-gp functionality is governed by the integrity of all ERM proteins in the recipient cell. This study identifies these candidate proteins as potential new therapeutic targets in circumventing MDR clinically. View Full-Text
Keywords: CD44; Ezrin-Radixin-Moesin; extracellular vesicles; multidrug resistance; P-glycoprotein CD44; Ezrin-Radixin-Moesin; extracellular vesicles; multidrug resistance; P-glycoprotein
Figures

Figure 1

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).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Pokharel, D.; Padula, M.P.; Lu, J.F.; Jaiswal, R.; Djordjevic, S.P.; Bebawy, M. The Role of CD44 and ERM Proteins in Expression and Functionality of P-glycoprotein in Breast Cancer Cells. Molecules 2016, 21, 290.

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]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top