ADP-ribosylation factor 1 (ARF1) takes part in cell proliferation and cell adhesion-mediated drug resistance (CAM-DR)

Cell adhesion-mediated drug resistance (CAM-DR) remains the primary obstacle in human multiple myeloma (MM) therapy. In this study, we aimed at investigating the expression and biologic function of ARF1 in MM. We determined that ARF1 expression was positively correlated with cell proliferation and k...

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Bibliographic Details
Published in:Annals of hematology 2017-05, Vol.96 (5), p.847-858
Main Authors: Xu, Xiaohong, Wang, Qiru, He, Yunhua, Ding, Linlin, Zhong, Fei, Ou, Yangyu, Shen, Yaodong, Liu, Hong, He, Song
Format: Article
Language:English
Subjects:
ADP-Ribosylation Factor 1 - genetics
ADP-Ribosylation Factor 1 - metabolism
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers
Cell Adhesion - genetics
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27 - metabolism
Drug Resistance, Neoplasm - genetics
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Silencing
Hematology
Humans
Male
Medicine
Medicine & Public Health
Middle Aged
Multiple Myeloma - diagnosis
Multiple Myeloma - drug therapy
Multiple Myeloma - genetics
Multiple Myeloma - mortality
Oncology
Original Article
Phosphorylation
Proportional Hazards Models
RNA Interference
Signal Transduction
Treatment Outcome
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Summary:Cell adhesion-mediated drug resistance (CAM-DR) remains the primary obstacle in human multiple myeloma (MM) therapy. In this study, we aimed at investigating the expression and biologic function of ARF1 in MM. We determined that ARF1 expression was positively correlated with cell proliferation and knockdown of ARF1 contributed to CAM-DR. The enhancement in the adhesion of MM cells to fibronectin (FN) or the bone marrow stroma cell line HS-5 cells translated to an increased CAM-DR phenotype. Importantly, we showed that this CAM-DR phenotype was correlated with the phosphorylation of Akt and ERK in MM cells. Moreover, we sought to determine whether ARF1 could interact with p27 in RPMI8226 cells. Knockdown of ARF1 also significantly decreased pT157-p27 protein expression in RPMI8226 cells. Our research shows ARF1 may reverse CAM-DR by regulating phosphorylation of p27 at T157 in MM. Taken together, our data shed new light on the molecular mechanism of CAM-DR in MM, and targeting ARF1 may be a novel therapeutic approach for improving the effectiveness of chemotherapy in MM.
ISSN:0939-5555
1432-0584
DOI:10.1007/s00277-017-2949-2