title: Reversion-inducing cysteine-rich protein with Kazal motifs and its regulation by glycogen synthase kinase 3 signaling in oral cancer.
abstract: The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and glycogen synthase kinase (GSK3) are novel tumor suppressors, and emerging evidence has suggested their active role in oral cancer pathogenesis. In the present study, 112 human samples, including 55 fresh samples of 14 adjacent normal tissues, 25 noninvasive oral tumors, and 18 invasive tumors, were included. The messenger RNA (mRNA) expression, protein expression, and promoter methylation of the RECK gene, as well as the expression of GSK3β, phospho/total β-catenin, and c-myc, were measured by RT-PCR, bisulphate modification-PCR, immunohistochemistry, and Western blot analysis. Additionally, ectopic expression of in/active GSK3β was performed in cell culture experiments. This study provided information on the progressive silencing of RECK gene expression at the protein and mRNA levels paralleled with promoter hypermethylation at various stages of oral tumor invasion. RECK expression and the hypermethylation of the RECK gene promoter were negatively and positively correlated with pS9GSK3β/c-myc expression, respectively. Further, a negative trend of RECK protein expression with nuclear β-catenin expression was observed. Induced expression of active GSK3β reversed the RECK silencing in SCC9 cells. Collectively, our results demonstrated that the silencing of the RECK gene, possibly regulated by the GSK3β pathway, is an important event in oral cancer invasion and this pathway could be exploited for therapeutic interventions.
authors.affiliation: Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India.
authors.forename: Kamdeo K
authors.initials: KK
authors.lastname: Pramanik
authors.affiliation: Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India.
authors.forename: Abhay K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India.
authors.forename: Manzar
authors.initials: M
authors.lastname: Alam
authors.affiliation: Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India.
authors.forename: Tanushree
authors.initials: T
authors.lastname: Kashyap
authors.affiliation: Centre for Applied Chemistry, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India.
authors.forename: Prajna
authors.initials: P
authors.lastname: Mishra
authors.affiliation: Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India.
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Panda
authors.affiliation: Centre for Applied Chemistry, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India.
authors.forename: Ratan K
authors.initials: RK
authors.lastname: Dey
authors.affiliation: Division of Surgical Oncology, Department of Surgery, College of Medicine, The University of Illinois at Chicago, 840 S. Wood Street, Suite 601 Clinical Sciences Building, MC 958, Chicago, IL, 60612, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Rana
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India.
authors.forename: Siddavaram
authors.initials: S
authors.lastname: Nagini
authors.affiliation: Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, Jharkhand, 835205, India. rajakishore.mishra@cuj.ac.in.
authors.forename: Rajakishore
authors.identifier: http://orcid.org/0000-0002-1735-2411
authors.initials: R
authors.lastname: Mishra
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C115460:RECK protein, human; D012333:RNA, Messenger; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: GSK3α/β; OSCC; Oral cancer invasion; Oral squamous cell carcinoma; RECK; c-Myc; β-Catenin