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.
|Numero di pagine||11|
|Rivista||Journal of Cellular Biochemistry|
|Stato di pubblicazione||Published - 2017|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
Di Bella, M. A., Alessandro, R., Anzanello, F., Chang, T. C., Chao, O. S., Goodman, O. B., Rappa, G., & Lorico, A. (2017). The HDAC6 Inhibitor tubacin induces release of CD133+ extracellular vesicles from cancer cells. Journal of Cellular Biochemistry, 118, 4414-4424.