Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivo
Open Access
- 24 December 2012
- journal article
- Published by Springer Science and Business Media LLC in Journal of Translational Medicine
- Vol. 10 (1), 254
- https://doi.org/10.1186/1479-5876-10-254
Abstract
Membrane-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. To 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. Treating 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. Therefore, PLSCR1 may serve as a potential therapeutic target for CRC.Keywords
This publication has 39 references indexed in Scilit:
- An Informatics-assisted Label-free Approach for Personalized Tissue Membrane Proteomics: Case Study on Colorectal CancerMolecular & Cellular Proteomics, 2011
- Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factorsBioinformatics, 2008
- Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cellsOncogene, 2006
- The Negative c-Myc Target Onzin Affects Proliferation and Apoptosis via Its Obligate Interaction with Phospholipid Scramblase IMolecular and Cellular Biology, 2006
- Phospholipid Scramblase 1 Binds to the Promoter Region of the Inositol 1,4,5-Triphosphate Receptor Type 1 Gene to Enhance Its ExpressionPublished by Elsevier BV ,2005
- Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growthAnnals of Oncology, 2002
- Regulation of β-Catenin Function by the IκB KinasesJournal of Biological Chemistry, 2001
- EGFR and cancer prognosisEuropean Journal Of Cancer, 2001
- Therapeutic monoclonal antibodies in oncology: an update: Monoclonal antibodies directed at growth factor receptorsAnnals Of Oncology, 2000
- ZD1839 (???Iressa???)*,??? as an Anticancer AgentDrugs, 2000