title: Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial-mesenchymal transition.
abstract: Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241-5253). We investigated the mechanisms by which SPRY regulates epithelial-mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3' untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1(-/-) and Spry2(-/-) double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.
authors.affiliation: Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Shim
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wright
authors.affiliation: Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, USA.
authors.forename: K
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Palka-Hamblin
authors.affiliation: Molecular Cytology Core, University of Missouri, Columbia, MO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jurkevich
authors.affiliation: Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, USA.|Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
authors.forename: S
authors.initials: S
authors.lastname: Khare
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C486055:SPRY1 protein, human; C485561:SPRY2 protein, human; C425468:Spry1 protein, mouse; C494921:AKT2 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C118389:Spry2 protein, mouse