NDLI: Reversion-inducing cysteine-rich protein with Kazal motifs and its regulation by glycogen synthase kinase 3 signaling in oral cancer

Content Provider	Springer Nature Link
Author	Pramanik, Kamdeo K. Singh, Abhay K. Alam, Manzar Kashyap, Tanushree Mishra, Prajna Panda, Aditya K. Dey, Ratan K. Rana, Ajay Nagini, Siddavaram Mishra, Rajakishore
Copyright Year	2016
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 pS$^{9}$GSK3β/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.
Starting Page	15253
Ending Page	15264
Page Count	12
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	11
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-09-30
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Oral squamous cell carcinoma Oral cancer invasion OSCC RECK GSK3α/β β-Catenin c-Myc Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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