title: Pyruvate kinase isoform M2 (PKM2) participates in multiple myeloma cell proliferation, adhesion and chemoresistance.
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.
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: He
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, Affiliated Hospital of Nantong University, Nantong University, Nantong 22600, Jiangsu Province, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Yuejiao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Yaxun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Qiru
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Chun
authors.initials: C
authors.lastname: Cheng
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009101:Multiple Myeloma / Q000201:enzymology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells; D013963:Thyroid Hormones / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases; D005353:Fibronectins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C436291:CDKN1B protein, human; C494918:AKT1 protein, human
keywords: CAM-DR; MAPK/ERK; MM; PI3K/Akt; PKM2; Proliferation