The role of SH3GL3 in myeloma cell migration/invasion, stemness and chemo-resistance.
Multiple myeloma (MM) is an incurable cancer characterized by clonal expansion of malignant plasma cells in the bone marrow and their egress into peripheral blood. The mechanisms of myeloma cells migration/invasion have remained unclear. Herein, we found SH3GL3 was highly expressed in the CD138-negative (CD138-) myeloma cells. The migration/invasion capability of CD138- cells was significantly higher than that in the CD138-positive (CD138+) cells. Silencing SH3GL3 using shRNA reduced myeloma cells migration/invasion. Conversely, overexpression of SH3GL3 increased myeloma cells migration/invasion. Moreover, SH3GL3 is also associated with the stemness and chemo-resistance of CD138- myeloma cells. Elevated expression of stem cell and multi-drug resistant markers were seen in the myeloma cells with overexpressed SH3GL3; while knocking-down SH3GL3 reduced the expression of these markers. A marked increase in p-PI3K and p-FAK was observed in the cells with overexpressed SH3GL3. To test if FAK/PI3K signaling pathway was involved in the SH3GL3-mediated myeloma cells migration, the cells transfected w/wo SH3GL3 cDNA were treated with FAK inhibitor 14 and PI3K inhibitor LY294002. Inhibition of FAK and PI3K attenuated SH3GL3-mediated migration /invasion. Our findings indicate that SH3GL3 plays an important role in myeloma cell migration/invasion, stemness and chemo-resistance. The SH3GL3-mediated myeloma cell migration/invasion is mediated by FAK/PI3K signaling pathway.
Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC27157, USA.
Ruoying
R
Chen
Department of Blood Transfusion, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
Hong
H
Zhao
Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC27157, USA.
Dan
D
Wu
Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC27157, USA.
Chen
C
Zhao
Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC27157, USA.
Weiling
W
Zhao
Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC27157, USA.|College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China.
Xiaobo
X
Zhou
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D015415:Biomarkers; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008954:Models, Biological; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053668:Syndecan-1 / Q000378:metabolism; D059467:Transcriptome
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C115574:SH3GL3 protein, human; D053668:Syndecan-1; D019869:Phosphatidylinositol 3-Kinases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt
CD138− cells; SH3GL3; chemo-resistance; migration/invasion; stemness
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