unexpected functions of slug (snai2), a master regulator of emt, in metastatic prostate cancer cell lines

slug (snai2), a regulator of epithelial-to-mesenchymal transition (emt), is a zinc finger transcription factor involved in neurulation. intriguingly, snai2 gene expression has been linked to the aggressiveness of neuroblastoma, melanoma and lung, colon, ovarian and breast carcinoma. of note, many metastatic cancers recapitulate emt to enhance cell motility and invasion. moreover, metastasis is the main cause of prostate cancer– related death. to investigate the role of slug in prostate cancer, we determined its expression by quantitative rt-pcr in normal prostate epithelial cells and carcinoma cell lines and then used an rnai strategy to investigate the function of slug in two selected carcinoma cell lines. among the prostate carcinoma cell lines, pc-3 and pc3-16 showed a moderate and the highest expression of slug, respectively. long-term knock-down of slug expression induced a severe decline in cell proliferation in both cell lines, with a prominent g0/g1 arrest in pc3-16 cells. apoptosis was slightly enhanced in pc-3 cells only. snai2 sirna-treated cells did not tolerate detachment from the culture plates, probably due to downregulation of integrin α6β4. moreover, suppression of slug expression strongly abolished invasiveness of pc-3 cells. finally, knock-down of slug expression disturbed both the microtubule and actin cytoskeletons resulting in grossly enlarged cells with a jellyfish-like phenotype. together, these data suggest that the most pertinent function of slug in prostate cancers that express it is to act as a regulator of cell adhesion and cell shape maintenance.