Abstract 2043: SATB1 (special AT-rich binding protein 1) as a putative therapeutic target in colorectal cancer

In this study, we have analyzed the function of SATB1 in primary and in established colorectal cancer cell lines and determined the therapeutic relevance of SATB1-specific gene knockdown approaches by RNA interference (RNAi). In CRC cells, an RNAi-mediated knockdown of the SATB1 was achieved by transient or by stable transfection with specific siRNAs or shRNAs-encoding plasmids, each leading to markedly reduced SATB1 mRNA and protein levels. SATB1 knockdown caused an inhibition of proliferation, a deceleration of cell cycle progression and pro-apoptotic effects. Further analyses revealed effects of SATB1 on multiple signaling pathways influencing e.g. EMT, apoptosis and ErbB receptor expression. The functional relevance of SATB1 (knockdown) was also determined in vivo in an s.c. tumor xenograft model in athymic nude mice, using stable LS174T knockdown cells. Notably, a marked inhibition of tumor growth was observed.Beyond stable established cell lines, studies were extended towards primary colorectal carcinoma cells. Transient siRNA-mediated SATB1 knockdown led to antiproliferative and proapoptotic effects in primary cell lines with different SATB1 expression levels. The therapeutic potential of SATB1 inhibition was further explored in vivo in mice bearing s.c. xenografts. For the induction of therapeutic RNAi in vivo, mice were treated with polymeric nanoparticles containing siRNAs, i.e., polyethylenimine (PEI)/siRNA-complexes. Notably, a marked inhibition of tumor growth wa...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research