Research Summary: HDAC Inhibition Decreases the Expression of EGFR in Colorectal Cancer Cells

ABSTRACT

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase which
promotes cell proliferation and survival, is abnormally overexpressed in
numerous tumors of epithelial origin, including colorectal cancer (CRC). EGFR
monoclonal antibodies have been shown to increase the median survival and are
approved for the treatment of colorectal cancer. Histone deacetylases (HDACs),
frequently overexpressed in colorectal cancer and several malignancies, are
another attractive targets for cancer therapy. Several inhibitors of HDACs
(HDACi) are developed and exhibit powerful antitumor abilities. In this study,
human colorectal cancer cells treated with HDACi exhibited reduced EGFR
expression, thereby disturbed EGF-induced ERK and Akt phosphorylation. HDACi
also decreased the expression of SGLT1, an active glucose transporter found to
be stabilized by EGFR, and suppressed the glucose uptake of cancer cells. HDACi
suppressed the transcription of EGFR and class I HDACs were proved to be
involved in this event. Chromatin immunoprecipitation analysis showed that HDACi
caused the dissociation of SP1, HDAC3 and CBP from EGFR promoter. Our data
suggested that HDACi could serve as a single agent to block both EGFR and HDAC,
and may bring more benefits to the development of CRC therapy.

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Publisher: Public Library of Science

Date Published: 25-March-2011

Author(s): Chou C., Wu M., Huang W., Chen C.

Link: https://doi.org/10.1371/journal.pone.0018087

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