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

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

DOI  :  10.1186/1479-5876-10-254

来源: DOAJ

【 摘 要 】

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

Therefore, PLSCR1 may serve as a potential therapeutic target for CRC.

【 授权许可】

Unknown