Activated ERM Protein Plays a Critical Role in Drug Resistance of MOLT4 Cells Induced by CCL25

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jan 18

PMID 23326330

Citations 15

Authors

Li Zhang

Ruijing Xiao

Jie Xiong

Jun Leng

Altaf Ehtisham

Yi Hu

Qianshan Ding

Hui Xu

Shengwu Liu

Jin Wang

Dean G Tang

Qiuping Zhang

Affiliations

Soon will be listed here.

Abstract

We have previously demonstrated that the CCR9/CCL25 signaling pathway plays an important role in drug resistance in human acute T-lymphocytic leukemia (T-ALL) by inducing activation of ERM protein with polarized distribution in T-ALL cell line MOLT4. However, the mechanism of action of the activated ERM protein in the drug resistance of MOLT4 cells induced by CCL25 remains uncharacterized. Here we investigated the mechanism of CCR9/CCL25-initiated drug resistance in CCR9-high-expressing T-ALL cells. Our results showed that 1) the function of P-gp was increased after treatment with CCL25; 2) P-gp colocalized and co-immunoprecipitated with p-ERM and F-actin in CCL25 treated cells; and 3) ERM-shRNA conferred drug sensitivity coincident with release of ERM interactions with P-gp and F-actin after treatment with CCL25. These data suggest it is pivotal that P-gp associate with the F-actin cytoskeleton through p-ERM in CCR9/CCL25 induced multidrug resistance of T-ALL cells. Strategies aimed at inhibiting P-gp-F-actin cytoskeleton association may be helpful in increasing the efficiency of therapies in T-ALL.

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