期刊
LEUKEMIA RESEARCH
卷 39, 期 12, 页码 1428-1436出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2015.09.019
关键词
PKM2; MM; Proliferation; CAM-DR; PI3K/Akt; MAPK/ERK
资金
- National Natural Science Foundation of China [81172879, 81201858, 81372537, 81373223, 81571616, 81570187]
- Natural Scientific Foundation of Jiangsu Province [BK2012231, BK20131206]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Cell adhesion mediated drug resistance (CAM-DR) remains the major barrier in human multiple myeloma (MM) therapy. In the present study, we aimed at investigating the role of pyruvate kinase isoform M2 (PKM2) in MM CAM-DR. We determined that PKM2 expression was positively correlated with cell proliferation and knockdown of PKM2 contributed to the increased cell adhesion rate in MM. The enhancement in the adhesion of MM cells to fibronectin 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. Taken together, our data shed new light on the molecular mechanism of CAM-DR in MM, and targeting PKM2 may be a novel therapeutic approach for improving the effectiveness of chemotherapy in MM. (C) 2015 Published by Elsevier Ltd.
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