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J Cell Biochem. 2017 Dec;118(12):4414-4424. doi: 10.1002/jcb.26095. Epub 2017 May 31.

The HDAC6 Inhibitor Tubacin Induces Release of CD133+ Extracellular Vesicles From Cancer Cells.

Author information

1
College of Medicine, Roseman University, Las Vegas, Nevada, 89135.
2
Amnis, Part of MilliporeSigma, Seattle, Washington, 98119.
3
Department of Biopathology and Medical Biotechnology, University of Palermo, Via Divisi 83, Palermo, Italy.
4
Roseman Cancer Center, Las Vegas, Nevada, 89135.

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. J. Cell. Biochem. 118: 4414-4424, 2017.

KEYWORDS:

CANCER; CD133; EXOSOMES; EXTRACELLULAR VESICLES; HDAC6; LIPID; TUBACIN

PMID:
28452069
DOI:
10.1002/jcb.26095
[Indexed for MEDLINE]

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