title: Reelin promotes the adhesion and drug resistance of multiple myeloma cells via integrin β1 signaling and STAT3.
abstract: Reelin is an extracellular matrix (ECM) protein that is essential for neuron migration and positioning. The expression of reelin in multiple myeloma (MM) cells and its association with cell adhesion and survival were investigated. Overexpression, siRNA knockdown, and the addition of recombinant protein of reelin were used to examine the function of reelin in MM cells. Clinically, high expression of reelin was negatively associated with progression-free survival and overall survival. Functionally, reelin promoted the adhesion of MM cells to fibronectin via activation of α5β1 integrin. The resulting phosphorylation of Focal Adhesion Kinase (FAK) led to the activation of Src/Syk/STAT3 and Akt, crucial signaling molecules involved in enhancing cell adhesion and protecting cells from drug-induced cell apoptosis. These findings indicate reelin's important role in the activation of integrin-β1 and STAT3/Akt pathways in multiple myeloma and highlight the therapeutic potential of targeting reelin/integrin/FAK axis.
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Liang
authors: L
authors: Lin
authors: Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors: Fan
authors: F
authors: Yan
authors: Jining No.1 People's Hospital, Jining, Shandong 272011, China.
authors: Dandan
authors: D
authors: Zhao
authors: Peking University Institute of Hematology, People's Hospital, Beijing 100044, China.
authors: Meng
authors: M
authors: Lv
authors: Hangzhou Cancer Hospital, Hang Zhou 310002, China.
authors: Xiaodong
authors: X
authors: Liang
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Hui
authors: H
authors: Dai
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Xiaodan
authors: X
authors: Qin
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Yan
authors: Y
authors: Zhang
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Jie
authors: J
authors: Hao
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Xiuyuan
authors: X
authors: Sun
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Yanhui
authors: Y
authors: Yin
authors: Peking University Institute of Hematology, People's Hospital, Beijing 100044, China.
authors: Xiaojun
authors: X
authors: Huang
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Jun
authors: J
authors: Zhang
authors: Peking University Institute of Hematology, People's Hospital, Beijing 100044, China.
authors: Jin
authors: J
authors: Lu
authors: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Qing
authors: Q
authors: Ge
mesh_terms: D002448:Cell Adhesion / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000091042:Reelin Protein; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000072377:Syk Kinase / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D000091042:Reelin Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C000606896:SYK protein, human; D000072377:Syk Kinase; D051057:Proto-Oncogene Proteins c-akt; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: STAT3; adhesion; integrin; multiple myeloma; reelin