title: Silencing HS6ST3 inhibits growth and progression of breast cancer cells through suppressing IGF1R and inducing XAF1.
abstract: Heparan sulfate 6-O-sulfation is biologically edited by 6-O-sulfotransferases (HS6STs) within heparan sulfate chains. Three isoforms of HS6ST have been identified. These enzymes are found to be differentially expressed in a variety of tissues. Recently, several studies have shown that dysregulation of 6-O-sulfotransferases could be involved in tumorigenesis of several cancers. This study aimed to analyze the expression and function of HS6ST3 in breast cancer. HS6ST3 was found up-regulated in T47D, MCF7 and MDA-MB231 breast cancer cell lines. HS6ST3 was then silenced in T47D and MCF7 using siRNA. Silencing HS6ST3 diminished tumor cell growth, migration and invasion, but enhanced cell adhesion and apoptosis in breast cancer. Gene microarray analysis revealed that silencing HS6ST3 significantly changed the expression of IGF1R and XAF1 in breast cancer cells. Further functional studies showed that the cellular processes were mediated by IGF1R and XAF1 after silencing HS6ST3 in breast cancer cells. Together these results indicate that HS6ST3 might be involved in the tumorigenesis of breast cancer and it could be a promising target in breast cancer therapy.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: antoi@nus.edu.sg.
authors.forename: Omid
authors.initials: O
authors.lastname: Iravani
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Boon-Huat
authors.initials: BH
authors.lastname: Bay
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: georgeyip@nus.edu.sg.
authors.forename: George Wai-Cheong
authors.initials: GW
authors.lastname: Yip
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics* / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C000597236:IGF1R protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D017451:Receptors, Somatomedin; C417551:XAF1 protein, human; D017526:Receptor, IGF Type 1; C000589146:HS6ST3 protein, human; D015238:Sulfotransferases
keywords: Breast cancer; Cell growth; Gene silencing; Heparan sulfate; Tumor progression