title: Role of SATB2 in human pancreatic cancer: Implications in transformation and a promising biomarker.
abstract: SATB2 (special AT-rich binding protein-2), a transcription factor and chromatin modulator, regulates the expression of genes required for maintaining pluripotency and self-renewal. The molecular mechanisms by which human pancreatic normal ductal epithelial cells are transformed to cancer cells are not well understood. The main goal of the paper is to examine the molecular mechanisms by which SATB2 regulates transformation of human pancreatic normal ductal epithelial (HPNE) cells, and assess whether transformed HPNE cells gained the phenotypes of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in pancreatic CSCs, primary tissues and cell lines, but not in HPNE cells. SATB2 induces cellular transformation, stemness and epithelial to mesenchymal transition in HPNE cells, and inhibition of its expression suppresses these activities. Overexpression of SATB2 in HPNE cells resulted in induction of stem cell markers (CD44, CD24 and CD133), and transcription factors (Oct4, Sox2 and Nanog). SATB2 can directly bind to promoters of Bcl-2, Bsp, Nanog, c-Myc, XIAP, Klf4 and Hoxa2, suggesting the role of SATB2 in pluripotency, cell survival and proliferation. SATB2-overexpressing HPNE cells (HPNE/SATB2) formed tumors in Balb C nude mice, whereas HPNE/Empty vector cells did not form any tumor. Since SATB2 is highly expressed in human pancreatic cancer tissues and cell lines, but not in HPNE cells and normal pancreatic tissue, it can drive pancreatic cancer growth and metastasis. Our findings suggest that SATB2 can induce dedifferentiation by inducing stemness and may have a role in pancreatic carcinogenesis, and can be used as a diagnostic biomarker.
authors.affiliation: Kansas City VA Medical Center, Kansas City, MO 66128, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Kansas City VA Medical Center, Kansas City, MO 66128, USA.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Kansas City VA Medical Center, Kansas City, MO 66128, USA.|Department of Pathology, University of Missouri-School of Medicine, Kansas City, MO 64108, USA.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Shankar
authors.affiliation: Kansas City VA Medical Center, Kansas City, MO 66128, USA.|Department of Pharmaceutical Sciences, University of Missouri-School of Medicine, Kansas City, MO 64108, USA.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D054337:Cell Dedifferentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000737:chemistry; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000090062:Kruppel-Like Factor 4; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000166:cytology; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002843:Chromatin; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors
keywords: SATB2; cancer stem cell; pancreatic cancer; pluripotency; stem cell