title: The effect of S1P receptor signaling pathway on the survival and drug resistance in multiple myeloma cells.
abstract: Multiple myeloma (MM) remains incurable by conventional chemotherapy. Sphingosine-1-phosphate (S1P) receptor-mediated signaling has been recently demonstrated to have critical roles in cell survival and drug resistance in a number of hematological malignancies. To dissect the roles of S1P receptor pathway in MM, we systematically examined cell viability and protein expression associated with cell survival and drug resistance in MM cell lines upon treatment with either pathway activator (S1P) or inhibitor (FTY720). Our results reveal that FTY720 inhibits cell proliferation by downregulating expression of target genes, while S1P has an opposite effect. Knocking down of S1P receptor S1P5R results in a reduction of cell survival-related gene expression; however, it does not have impacts on expression of drug resistance genes. These results suggest that S1P signaling plays a role in cell proliferation and drug resistance in MM, and targeting this pathway will provide a new therapeutic direction for MM management.
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China.
authors: Di
authors: D
authors: Fu
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China.
authors: Yingchun
authors: Y
authors: Li
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China.
authors: Jia
authors: J
authors: Li
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China.
authors: Xiaoyan
authors: X
authors: Shi
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China.
authors: Ronghui
authors: R
authors: Yang
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China.
authors: Yuan
authors: Y
authors: Zhong
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China.
authors: Huihan
authors: H
authors: Wang
authors: Department of Hematology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110021, Liaoning, China. liaoaj@sj-hospital.org.
authors: Aijun
authors: A
authors: Liao
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009363:Neoplasm Proteins; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride
keywords: Cell survival; Drug resistance; Multiple myeloma (MM); Sphingosine-1-phosphate (S1P); Sphingosine-1-phosphate receptors (S1PRs)