We aimed to elucidate the effect of herbimycin A (HMA), a heat shock protein 90 inhibitor, on cell growth and epithelial-mesenchymal transition (EMT) in anaplastic thyroid carcinoma (ATC) cells. HMA inhibited cell growth and migration concomitantly with increase of E-cadherin as well as decrease of N-cadherin and vimentin. Moreover, HMA upregulated p21 and p27, while it downregulated p53 and Akt. In HMA-treated condition, knockdown of E-cadherin and overexpression of p53 increased N-cadherin and vimentin, and mitigated the inhibitory effects of HMA on cell growth and migration. Furthermore, knockdown of p21 and p27 ameliorated inhibition of cell growth and reversal of EMT. In addition, the activation of Akt attenuated growth inhibition, cell death and EMT reversal. Therefore, we propose that HMA suppresses cell growth, and reverses EMT in conjunction with the activation of E-cadherin, p21 and p27 and the inactivation of p53 and PI3K/Akt signaling in ATC cells. (C) 2014 Elsevier Inc. All rights reserved.