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Annals of Hematology

, Volume 96, Issue 5, pp 847–858 | Cite as

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

  • Xiaohong Xu
  • Qiru Wang
  • Yunhua He
  • Linlin Ding
  • Fei Zhong
  • Yangyu Ou
  • Yaodong Shen
  • Hong Liu
  • Song He
Original Article

Abstract

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.

Keywords

Multiple myeloma ARF1 p27 Proliferation CAM-DR 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81372537, 81570187, 81070400).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Xiaohong Xu
    • 1
  • Qiru Wang
    • 2
  • Yunhua He
    • 2
  • Linlin Ding
    • 2
  • Fei Zhong
    • 2
  • Yangyu Ou
    • 2
  • Yaodong Shen
    • 2
  • Hong Liu
    • 3
    • 4
  • Song He
    • 5
  1. 1.Department of OncologyAffiliated Cancer Hospital of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical CollegeNantong UniversityNantongPeople’s Republic of China
  3. 3.Department of HematologyAffiliated Hospital of Nantong University, Nantong UniversityNantongPeople’s Republic of China
  4. 4.Department of HematologyAffiliated Hospital of Nantong University, Nantong UniversityNantongChina
  5. 5.Department of PathologyAffiliated Cancer Hospital of Nantong UniversityNantongPeople’s Republic of China

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