title: Lowered Expression of Tumor Suppressor Candidate MYO1C Stimulates Cell Proliferation, Suppresses Cell Adhesion and Activates AKT.
abstract: Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.
authors.affiliation: School of Bioscience, Tumor Biology research group, University of Skövde, SE-541 28, Skövde, Sweden.|Department of Medical and Clinical Genetics, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Gothenburg, Sweden.
authors.forename: Kittichate
authors.initials: K
authors.lastname: Visuttijai
authors.affiliation: Department of Medical and Clinical Genetics, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Gothenburg, Sweden.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pettersson
authors.affiliation: School of Bioscience, Tumor Biology research group, University of Skövde, SE-541 28, Skövde, Sweden.
authors.forename: Yashar
authors.initials: Y
authors.lastname: Mehrbani Azar
authors.affiliation: Department of physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, 0007, South Africa.
authors.forename: Iman
authors.initials: I
authors.lastname: van den Bout
authors.affiliation: Department of Pathology, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Örndal
authors.affiliation: Department of Obstetrics and Gynecology, Halland Hospital Varberg, SE- 432 37, Varberg, Sweden.
authors.forename: Janusz
authors.initials: J
authors.lastname: Marcickiewicz
authors.affiliation: Institute of Mathematical Statistics, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Science and Technology, University of Linköping, ITN, SE-601 74, Norrköping, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Hörnquist
authors.affiliation: School of Bioscience, Tumor Biology research group, University of Skövde, SE-541 28, Skövde, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Olsson
authors.affiliation: School of Bioscience, Tumor Biology research group, University of Skövde, SE-541 28, Skövde, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ejeskär
authors.affiliation: School of Bioscience, Tumor Biology research group, University of Skövde, SE-541 28, Skövde, Sweden.
authors.forename: Afrouz
authors.identifier: http://orcid.org/0000-0003-2525-3752
authors.initials: A
authors.lastname: Behboudi
mesh_terms: D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D024461:Myosin Type I / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D024461:Myosin Type I; C460367:MYO1C protein, human