The HDAC6 Inhibitor tubacin induces release of CD133+ extracellular vesicles from cancer cells

Riccardo Alessandro, Maria Antonietta Di Bella, Fabio Anzanello, Tim C. Chang, Olivia S. Chao, Oscar B. Goodman, Germana Rappa, Aurelio Lorico

Risultato della ricerca: Articlepeer review

12 Citazioni (Scopus)

Abstract

Tumor-derived extracellular vesicles (EVs) are emerging as an important mode of intercellular communication, capable of transferring biologically active molecules that facilitate the malignant growth and metastatic process. CD133 (Prominin-1), a stem cell marker implicated in tumor initiation, differentiation and resistance to anti-cancer therapy, is reportedly associated with EVs in various types of cancer. However, little is known about the factors that regulate the release of these CD133+ EVs. Here, we report that the HDAC6 inhibitor tubacin promoted the extracellular release of CD133+ EVs from human FEMX-I metastatic melanoma and Caco-2 colorectal carcinoma cells, with a concomitant downregulation of intracellular CD133. This effect was specific for tubacin, as inhibition of HDAC6 deacetylase activity by another selective HDAC6 inhibitor, ACY-1215 or the pan-HDAC inhibitor trichostatin A (TSA), and knockdown of HDAC6 did not enhance the release of CD133+ EVs. The tubacin-induced EV release was associated with changes in cellular lipid composition, loss of clonogenic capacity and decrease in the ability to form multicellular aggregates. These findings indicate a novel potential anti-tumor mechanism for tubacin in CD133-expressing malignancies.
Lingua originaleEnglish
pagine (da-a)4414-4424
Numero di pagine11
RivistaJournal of Cellular Biochemistry
Volume118
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

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