Role of stomatin-like protein 2 in colorectal cancer tumorigenesis via alteration of TGF-β1/Smad4 signaling


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David Lazenby, Kaimo Chen, Rongtao Zhang, Judy Ge, Guowei Liang, Matt Liu, Daeho Shie 1*
Author Affiliations
∗Correspondence author e-mail: MaoZ@uni.mis.edu: 1Department of Surgery, University of Colorado, United States

 

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death in the US, resulting in over a half-million deaths annually. Stomatin-like protein 2 (SLP-2) is a novel member of the stomatin superfamily and is found in several types of human tumors. However, whether it is expressed in human CRC is unknown. Recently, the importance of SMAD4, a downstream regulator in the TGF-beta signaling pathway, in colorectal cancer has been highlighted.TGF-beta signaling occurs through Smads 2/3/4, which translocate to the nucleus to regulate transcription; TGF-beta has tumor-suppressive effects in some tumor models and pro-metastatic effects in others. In patients with colorectal cancer (CRC), mutations or reduced levels of Smad4 have been correlated with reduced survival. A total of 93 patients with CRC was examined. In the present study, we aimed to explore the diagnostic value of SLP-2 in patients with CRC and to investigate whether CRC expression is regulated by transforming growth factor-β (TGF-β)/SMAD4 signaling. The expression of SLP-2 mRNA and protein was examined by immunohistochemistry (IHC) and qPCR, respectively. A standard immunohistochemical method was applied to stain the slides for hematoxylin and eosin (H&E), Tunnel, Phospho-Smad, E-cadherin, and β-catenin. Our data, revealed for the first time the role of  SLP-2 overexpression CRC through downregulation of Smad4. Thus, the loss of Smad4 in colorectal cancer appears to switch TGF-β from tumor suppressor to a tumor promoter, and this group of patients could potentially benefit from SLP-2 inhibitor therapy. Furthermore; present study suggest that  SLP-2 may be considered as a useful diagnostic marker for metastatic CRC.

Keywords: Colorectal cancer; SLP-2;  transforming growth factor-β; Smad 4; Immunohistochemistry

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.

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Research Article
DOI: http://dx.doi.org/10.18081/2333-5106/015-1/365-377
American Journal of BioMedicine 2015, Volume 3, Issue 1, pages 65-77
Received November 12, 2014; Accepted February 22, 2015, Published March 25, 2015

How to cite this article
Lazenby D, Chen K, Zhang R, Ge J, Liang G, Liu M, Shie D. Role of stomatin-like protein 2 in colorectal cancer tumorigenesis via alteration of TGF-β1/Smad4 signaling. American Journal of BioMedicine 2015;3(1):365-377
Research article
1. Abstract
2. Keywords
3. Introduction
5. Results
6. Discussion
7. References

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