Abstract Collapsin response mediator protein 1 (CRMP1) is originally identified and characterized as a cytoplasmic phosphoprotein involved in the Semaphorin 3A (Sema3A)-regulated growth cone collapse during neural development, via its regulation of cytoskeleton dynamics, and then also characterized as an invasion suppressor in lung cancer. Thus, we hypothesize that CRMP1 may be involved in the epithelial-mesenchymal transition (EMT) process and invasion or metastasis via its regulation on cytoskeleton organization in prostate cancer cells. Results of immunohistochemistry study showed that CRMP1 exhibited a reduced expression pattern in high Gleason-scored clinical prostate cancer tissues. In vitro functional studies showed that stable CRMP1-knockdown could induce EMT in prostate cancer cells (DU145), while its ectopic expression could induce the reverse process mesenchymal-epithelial transition (MET) in both DU145 and PC-3 prostate cancer cells, as evidenced by significant change of cellular morphology and altered expression levels of epithelial and mesenchymal markers. Confocal immunofluorescence showed that reorganization of F-actin was seen after shRNA-mediated CRMP1-knockdown in DU145 cells. It was also revealed that CRMP1 overexpression could confer the resistance to TGF-β1- and Snail-induced EMT in prostate cells. Results of CRMP1 promoter-driven luciferase reporter and ChIP assays indicated that Snail was a direct transrepressor of CRMP1 gene, which showed a downregulation pattern in both prostate cancer cells (DU145) and immortalized prostatic epithelial cells (BPH1) with overexpression of Snail. Furthermore, wound healing and Matrigel invasion assays showed that CRMP1 could inhibit cell migration and invasion capacity in DU145 and PC-3 cells. Taken together, our findings suggest that CRMP1 could play a role in prostate cancer invasion and metastasis, via its regulation on EMT and MET process. (This work was supported by a Direct Grant for Research and a RGC-GRF grant 2009/2010) Citation Format: Ganhui Cai, Shan Yu, Yanping Ji, Franky Leung Chan. CRMP1 functions to suppress epithelial-mesenchymal transition and invasion capacity of prostate cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C15.