Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivo

Journal of Translational Medicine

Research

Yeh-Pin Chou¹  Chung-Wei Fan²  Chia-Rui Shen³  Err-Cheng Chan³  Kuei-Tien Chen³  Yung-Bin Kuo³  Wei-Shan Wei⁴  Chun-Yu Chen⁵  Ya-Shan Chen⁵ 

[1] College of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan;Department of Colorectal Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan;College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan;Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan;Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan;

关键词: Phospholipid scramblase 1;    Retinoblastoma dephosphorylation;    Cyclin D1;    Cell cycle G1/S arrest;    Colorectal carcinomas;   

DOI  :  10.1186/1479-5876-10-254

 received in 2012-10-21, accepted in 2012-12-19,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMembrane-bound phospholipid scramblase 1 (PLSCR1) is involved in both lipid trafficking and cell signaling. Previously, we showed that PLSCR1 is overexpressed in many colorectal carcinomas (CRCs). In the present study, we investigated the tumorigenic role of PLSCR1 in CRC and suggest that it is a potential therapeutic target.MethodsTo identify PLSCR1 as a therapeutic target, we studied the tumorigenic properties of CRC cell lines treated with a monoclonal antibody (NP1) against the N-terminus of PLSCR1 in vitro and in vivo. We also investigated cell cycle status and epidermal growth factor receptor–related pathways and downstream effectors of PLSCR1 after blocking its function with NP1.ResultsTreating CRC cells with NP1 in vitro and in vivo decreased cell proliferation, anchorage-independent growth, migration, and invasion. Adding NP1 to the CRC cell line HT29 caused arrest at G1/S. Treating HT29 cells with NP1 significantly decreased the expression of cyclin D1 and phosphorylation levels of Src, the adaptor protein Shc, and Erks. The reduced level of cyclin D1 led to an increase in the activated form of the tumor suppressor retinoblastoma protein via dephosphorylation. These actions led to attenuation of tumorigenesis.ConclusionsTherefore, PLSCR1 may serve as a potential therapeutic target for CRC.

【 授权许可】

Unknown   
© Fan et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.