title: Activated ERM protein plays a critical role in drug resistance of MOLT4 cells induced by CCL25.
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.
authors: Department of Immunology, School of Basic Medical Science, Wuhan University, Wuhan, China.
authors: Li
authors: L
authors: Zhang
authors: Ruijing
authors: R
authors: Xiao
authors: Jie
authors: J
authors: Xiong
authors: Jun
authors: J
authors: Leng
authors: Altaf
authors: A
authors: Ehtisham
authors: Yi
authors: Y
authors: Hu
authors: Qianshan
authors: Q
authors: Ding
authors: Hui
authors: H
authors: Xu
authors: Shengwu
authors: S
authors: Liu
authors: Jin
authors: J
authors: Wang
authors: Dean G
authors: DG
authors: Tang
authors: Qiuping
authors: Q
authors: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019742:Chemokines, CC / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034622:RNA Interference; D054388:Receptors, CCR / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099149:Ezrin
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000199:Actins; D000903:Antibiotics, Antineoplastic; D019742:Chemokines, CC; D003598:Cytoskeletal Proteins; D004317:Doxorubicin; D008565:Membrane Proteins; D008840:Microfilament Proteins; D054388:Receptors, CCR; D000099149:Ezrin; C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; C071058:moesin; C071776:radixin