Pyruvate kinase isoform M2 (PKM2) participates in multiple myeloma cell proliferation, adhesion and chemoresistance

Yunhua He; Yuchan Wang; Hong Liu; Xiaohong Xu; Song He; Jie Tang; Yuejiao Huang; Xiaobing Miao; Yaxun Wu; Qiru Wang; Chun Cheng

doi:10.1016/j.leukres.2015.09.019

Pyruvate kinase isoform M2 (PKM2) participates in multiple myeloma cell proliferation, adhesion and chemoresistance

Leuk Res. 2015 Dec;39(12):1428-36. doi: 10.1016/j.leukres.2015.09.019. Epub 2015 Sep 28.

Authors

Yunhua He¹, Yuchan Wang¹, Hong Liu², Xiaohong Xu³, Song He⁴, Jie Tang¹, Yuejiao Huang⁴, Xiaobing Miao⁴, Yaxun Wu⁴, Qiru Wang¹, Chun Cheng⁵

Affiliations

¹ Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
² Department of Hematology, Affiliated Hospital of Nantong University, Nantong University, Nantong 22600, Jiangsu Province, People's Republic of China.
³ Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
⁴ Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
⁵ Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: ntchengchun@sina.com.

PMID: 26453405
DOI: 10.1016/j.leukres.2015.09.019

Abstract

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.

Keywords: CAM-DR; MAPK/ERK; MM; PI3K/Akt; PKM2; Proliferation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / biosynthesis
Carrier Proteins / genetics
Carrier Proteins / physiology*
Cell Adhesion
Cell Division
Cell Line, Tumor
Coculture Techniques
Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
Cyclin-Dependent Kinase Inhibitor p27 / genetics
Drug Resistance, Neoplasm
Extracellular Signal-Regulated MAP Kinases / metabolism
Fibronectins
Gene Expression Regulation, Neoplastic
Humans
Membrane Proteins / biosynthesis
Membrane Proteins / genetics
Membrane Proteins / physiology*
Multiple Myeloma / enzymology*
Multiple Myeloma / pathology
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Phenotype
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
RNA, Small Interfering / genetics
Signal Transduction / physiology
Stromal Cells
Thyroid Hormone-Binding Proteins
Thyroid Hormones / biosynthesis
Thyroid Hormones / genetics
Thyroid Hormones / physiology*

Substances

CDKN1B protein, human
Carrier Proteins
Fibronectins
Membrane Proteins
Neoplasm Proteins
RNA, Small Interfering
Thyroid Hormones
Cyclin-Dependent Kinase Inhibitor p27
Phosphatidylinositol 3-Kinases
AKT1 protein, human
Proto-Oncogene Proteins c-akt
Extracellular Signal-Regulated MAP Kinases