title: GPCR48/LGR4 promotes tumorigenesis of prostate cancer via PI3K/Akt signaling pathway.
abstract: G-protein-coupled receptor (GPCR) 48, also known as leucine-rich repeat-containing G-protein-coupled receptor (LGR) 4, is an orphan receptor belonging to the GPCR superfamily, which plays an important role in the development of various organs and multiple cancers. However, the function of GPCR48/LGR4 in prostate cancer has not been fully investigated. Herein, GPCR48/LGR4 was overexpressed and silenced in prostate cancer cells via plasmid and shRNA transfection, respectively. The expression of GPCR48/LGR4 in mRNA and protein levels was analyzed using RT-qPCR and Western blotting, respectively. Subsequently, we demonstrated the effects of GPCR48/LGR4 on the migration, invasion, proliferation and apoptosis of prostate cancer cells, including Du145 and PC-3 cells. Next, we investigated the relationship between GPCR48/LGR4 and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway. The results showed that the overexpression of GPCR48/LGR4 was associated with the up-regulation of Akt, a key effector of PI3K/Akt signaling pathway, which meantime up-regulated the expression of mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3β (GSK-3β), while down-regulated forkhead box, class O (FOXO), all of whom are the downstream targets of PI3K/Akt signaling pathway. Hence, the results suggested that GPCR48/LGR4 may regulate prostate cancer cells and tumor growth via the PI3K/Akt signaling pathway and could provide a better therapeutic target for the diagnosis and treatment of prostate cancer.
authors: Department of Oncology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
authors: Fang
authors: F
authors: Liang
authors: Junmin
authors: J
authors: Yue
authors: Junyong
authors: J
authors: Wang
authors: Lijuan
authors: L
authors: Zhang
authors: Rui
authors: R
authors: Fan
authors: Hao
authors: H
authors: Zhang
authors: Qingsong
authors: Q
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D043562:Receptors, G-Protein-Coupled; D058570:TOR Serine-Threonine Kinases; C411562:LGR4 protein, human; C546842:MTOR protein, human; C000605506:GSK3B protein, human; C000605507:Gsk3b protein, mouse
references: Sci STKE. 2004 Jan 13;2004(216):re2
references: 14734786
references: Stem Cells. 2013 Nov;31(11):2492-505
references: 23897697
references: Dev Dyn. 2009 Apr;238(4):993-1000
references: 19301403
references: Wiley Interdiscip Rev Syst Biol Med. 2014 Jan-Feb;6(1):115-23
references: 24741711
references: Curr Med Chem. 2011;18(36):5528-44
references: 22172063
references: Mol Cell Biol. 2001 Dec;21(24):8385-97
references: 11713275
references: Mol Endocrinol. 1998 Dec;12(12):1830-45
references: 9849958
references: Nihon Rinsho. 2014 Dec;72(12):2212-6
references: 25518360
references: Cancer Treat Rev. 2004 Apr;30(2):193-204
references: 15023437
references: Carcinogenesis. 2013 Dec;34(12):2861-9
references: 23803691
references: Mol Endocrinol. 2000 Feb;14(2):272-84
references: 10674399
references: Development. 2009 Aug;136(16):2747-56
references: 19605502
references: Int J Clin Oncol. 2003 Aug;8(4):193-9
references: 12955573
references: Nat Rev Genet. 2009 Jun;10(6):353-8
references: 19434079
references: Blood. 2003 Jan 1;101(1):236-44
references: 12393431
references: Mol Pharmacol. 2007 Jul;72(1):73-85
references: 17430995
references: Asian Pac J Cancer Prev. 2013;14(8):4775-8
references: 24083742
references: Int J Colorectal Dis. 2010 May;25(5):583-90
references: 20195621
references: Clin Cancer Res. 2002 Jul;8(7):2399-405
references: 12114445
references: Pharmacol Ther. 2014 May;142(2):164-75
references: 24333502
references: Exp Cell Res. 2014 May 15;324(1):75-83
references: 24704462
references: Cell. 2012 Apr 13;149(2):274-93
references: 22500797
references: Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6081-6
references: 18424556
references: Nat Rev Cancer. 2007 Feb;7(2):79-94
references: 17251915
references: Curr Opin Oncol. 2003 May;15(3):217-21
references: 12778015
references: J Proteome Res. 2011 Oct 7;10(10):4373-87
references: 21854069
references: J Urol. 2003 Dec;170(6 Pt 2):S65-7; discussion S67-8
references: 14610413
references: J Biol Chem. 2005 Mar 25;280(12):11583-9
references: 15653681
references: Virchows Arch. 2012 Oct;461(4):355-65
references: 22855134
references: Dev Biol. 2006 Feb 15;290(2):421-34
references: 16406039
references: Anticancer Drugs. 2009 Feb;20(2):83-8
references: 19065106
references: Cancer Res. 2006 Dec 15;66(24):11623-31
references: 17178856
references: Ann Surg Oncol. 2011 Apr;18(4):1166-74
references: 21125339