title: Upregulation of SATB1 is associated with prostate cancer aggressiveness and disease progression.
abstract: Disease aggressiveness remains a critical factor to the progression of prostate cancer. Transformation of epithelial cells to mesenchymal lineage, associated with the loss of E-cadherin, offers significant invasive potential and migration capability. Recently, Special AT-rich binding protein (SATB1) has been linked to tumor progression. SATB1 is a cell-type restricted nuclear protein, which functions as a tissue-specific organizer of DNA sequences during cellular differentiation. Our results demonstrate that SATB1 plays significant role in prostate tumor invasion and migration and its nuclear localization correlates with disease aggressiveness. Clinical specimen analysis showed that SATB1 was predominantly expressed in the nucleus of high-grade tumors compared to low-grade tumor and benign tissue. A progressive increase in the nuclear levels of SATB1 was observed in cancer tissues compared to benign specimens. Similarly, SATB1 protein levels were higher in a number of prostate cancer cells viz. HPV-CA-10, DU145, DUPro, PC-3, PC-3M, LNCaP and C4-2B, compared to non-tumorigenic PZ-HPV-7 cells. Nuclear expression of SATB1 was higher in biologically aggressive subclones of prostate cancer cells with their respective parental cell lines. Furthermore, ectopic SATB1 transfection conferred increased cell motility and invasiveness in immortalized human prostate epithelial PZ-HPV-7 cells which correlated with the loss of E-cadherin expression. Consequently, knockdown of SATB1 in highly aggressive human prostate cancer PC-3M cells inhibited invasiveness and tumor growth in vivo along with increase in E-cadherin protein expression. Our findings demonstrate that SATB1 has ability to promote prostate cancer aggressiveness through epithelial-mesenchymal transition.
authors: Department of Urology, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors: Sanjeev
authors: S
authors: Shukla
authors: Haripaul
authors: H
authors: Sharma
authors: Ata
authors: A
authors: Abbas
authors: Gregory T
authors: GT
authors: MacLennan
authors: Pingfu
authors: P
authors: Fu
authors: David
authors: D
authors: Danielpour
authors: Sanjay
authors: S
authors: Gupta
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D015820:Cadherins / Q000172:deficiency / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000235:genetics; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006801:Humans; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D036961:Matrix Attachment Region Binding Proteins; D034741:RNA, Small Interfering; C076189:SATB1 protein, human