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

Patients with colorectal cancer (CRC) possess a poor prognosis due to high rates of recurrence and metastasis. Although mechanisms of CRC tumorigenesis have been extensively studied, the pathogenesis of the disease is still not fully understood. Thus, further investigation on mechanisms involved in CRC occurrence is urgently needed. Genetic mutation, particularly alteration of tumor suppressors, is one of the most important early events in colorectal cancer (CRC) tumorigenesis. Besides, gene silencing via hypermethylation also plays a pivotal role. Emerging evidence has indicated that altered expression of membrane proteins (MPs) is intimately involved in tumorigenesis, but their role in CRC is largely unexplored. Stomatin-like protein 2 (SLP-2) is one of the best-characterized MPs. SLP-2 functions as a chaperone-like protein in early mitochondrial biogenesis and assembly of the respiratory chain complexes. SLP-2 was localized to the inner mitochondrial membrane, where it exerts important roles in regulating mitochondrial morphology and biogenesis, but its role in tumorigenesis remains unknown. Emerging evidence has demonstrated that alteration of mitochondrial dynamics is closely linked with tumorigenesis. Mitochondria exhibit highly dynamic morphology characterized by a continual process of fission and fusion. Accumulating findings indicate that mitochondrial dynamics are aberrant in different cancers. Aberrant fusion is detected in many cancers, while dysregulated fission is more associated with specific types of cancers. This study examined the role of SLP-2 in CRC tumorigenesis via alteration of TGF-β1/Smad4 signaling. SLP-2 expression was significantly reduced in CRC tissues, and its downregulation was associated with poor prognosis. Using gain- and loss-of-function methods, it was demonstrated that SLP-2 plays an essential role in inhibiting CRC cell migration and invasion in vitro and in vivo. Further studies revealed that SLP-2 suppressed TGF-β1-induced epithelial-mesenchymal transition and CRC cell invasion and migration by modulating the stability of Smad4.

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

Copyright © 2016 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 2016, Volume 4, Issue 2, pages 70-90
Received December 11, 2015; Accepted March 09, 2016; Published April 02, 2016

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 2016;4(2):70-90
Research article
1. Abstract
2. Keywords
3. Introduction
5. Results
6. Discussion
7. References

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