The role of SH3GL3 in myeloma cell migration/invasion, stemness and chemo-resistance
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Ruoying Chen1, Hong Zhao2, Dan Wu1, Chen Zhao1, Weiling Zhao1, Xiaobo Zhou1,3
1Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA
2Department of Blood Transfusion, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
3College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China
Xiaobo Zhou, email: [email protected]
Keywords: CD138− cells, SH3GL3, migration/invasion, stemness, chemo-resistance
Received: January 31, 2016 Accepted: September 12, 2016 Published: September 24, 2016
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.
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