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 Shi

AJBM  Volume 2, Issue 4, pages 432–447, April 2014             Full Text-PDF


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


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