title: A role for activator of G-protein signaling 3 (AGS3) in multiple myeloma.
abstract: 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.
authors.affiliation: Department of Hematology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shao
authors.forename: Xianting
authors.initials: X
authors.lastname: Huang
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Wang
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.forename: Zongmei
authors.initials: Z
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.forename: Yuejiao
authors.initials: Y
authors.lastname: Huang
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C525615:GPSM1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D004317:Doxorubicin