A role for activator of G-protein signaling 3 (AGS3) in multiple myeloma

Previous studies have demonstrated that activator of G-protein signaling 3 (AGS3; also known as GPSM1), a member of the AGS family, plays an important anti-apoptotic role through enhancing the phosphorylation of cyclic AMP response element-binding protein (p-CREB). In this report, we delineate the a...

Full description

Saved in:
Bibliographic Details
Published in:International journal of hematology 2014-01, Vol.99 (1), p.57-68
Main Authors: Shao, Shan, Huang, Xianting, Wang, Yuchan, He, Song, Xu, Xiaohong, Zhu, Xinghua, Yang, Xiaojing, Ding, Zongmei, Yao, Li, Huang, Yuejiao, Wang, Chun
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - pharmacology
Apoptosis - drug effects
Apoptosis - genetics
Biological and medical sciences
Cell Adhesion - drug effects
Cell Adhesion - genetics
Cell Line, Tumor
Cell Proliferation - drug effects
Doxorubicin - pharmacology
Drug Resistance, Neoplasm - genetics
Gene Expression Regulation, Neoplastic - drug effects
Guanine Nucleotide Dissociation Inhibitors - genetics
Guanine Nucleotide Dissociation Inhibitors - metabolism
Hematologic and hematopoietic diseases
Hematology
Humans
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunopathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Medicine
Medicine & Public Health
Multiple Myeloma - genetics
Multiple Myeloma - metabolism
Oncology
Original Article
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Previous studies have demonstrated that activator of G-protein signaling 3 (AGS3; also known as GPSM1), a member of the AGS family, plays an important anti-apoptotic role through enhancing the phosphorylation of cyclic AMP response element-binding protein (p-CREB). In this report, we delineate the anti-apoptotic role of AGS3 in multiple myeloma (MM). To do this, we developed a cell apoptotic model induced by doxorubicin in MM. Our data indicate that decreased expression of AGS3 is correlated with reduced levels of p-CREB in the apoptotic model. The negative role of AGS3 in cell apoptosis was further confirmed by knocking down AGS3. The microenvironment has been shown to influence tumor cell phenotype in response to chemotherapy. Since cell adhesion-mediated drug resistance remains a major obstacle for successful treatment of MM, we constructed a cell adhesion model in MM and detected the changing of AGS3 protein expression. AGS3 siRNA reversed the high rate of MM cell adhesion to either fibronectin or HS-5 cells. Consistent with the reduced adhesion rate, the cells also exhibited reduced drug resistance to doxorubicin, mitoxantrone, and dexamethasone. Collectively, these data indicate that AGS3 may be represented as a good candidate for pursuing clinical trials in MM. Moreover, our data provide a clinical therapeutic target for MM and potentially other tumors that home and/or metastasize to the bone.
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-013-1484-8