title: SRD5A2 gene expression inhibits cell migration and invasion in prostate cancer cell line via F-actin reorganization.
abstract: Steroid 5-alpha reductase type 2 (SRD5A2) gene is important for normal development and functioning of prostate gland but it is reported to be silenced in metastatic prostate cancer. We showed that exogenous SRD5A2 expression in prostate cancer cell line reduced cell migration and invasion. Additionally, the stable transfectants showed enhanced adhesion to the matrix accompanied by changes in cytoskeletal organization, involving actin polymerization. siRNA knockdown of the endogenous SRD5A2 mRNA in LnCAP cells was effective, it reversed the phenotype, and thus induced cell motility. The MEK1 and pERK1/2 levels were found to be reduced in SRD5A2-expressing cells. Further, the reduced level of p38 protein was correlated with low expression of MMP-2 and MMP-7 genes. The results suggest that SRD5A2 controls cell migration by indirectly regulating ERK/MAPK pathway.
authors.affiliation: National Centre for Human Genome Studies and Research, Panjab University, Chandigarh, 160014, India.
authors.forename: Suruchi
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: National Centre for Human Genome Studies and Research, Panjab University, Chandigarh, 160014, India.
authors.forename: Minu
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Systems Biology, Panjab University, Chandigarh, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.affiliation: National Centre for Human Genome Studies and Research, Panjab University, Chandigarh, 160014, India. tmukhopa@hotmail.com.
authors.forename: Tapas
authors.initials: T
authors.lastname: Mukhopadhyay
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human
keywords: Actin cytoskeleton; Invasion; Migration; Prostate cancer; SRD5A2