27-Hydroxycholesterol increases Myc protein stability via suppressing PP2A, SCP1 and FBW7 transcription in MCF-7 breast cancer cells

27-hydroxycholesterol (27-HC), the most abundant metabolite of cholesterol, is a risk factor for breast cancer. It can increase the proliferation of breast cancer cells and promote the metastasis of breast tumours in mouse models. Myc is a critical oncoprotein overexpressed in breast cancer. However...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2016-11, Vol.480 (3), p.328-333
Main Authors: Ma, Li-Ming, Liang, Zi-Rui, Zhou, Ke-Ren, Zhou, Hui, Qu, Liang-Hu
Format: Article
Language:English
Subjects:
27-Hydroxycholesterol
60 APPLIED LIFE SCIENCES
Breast cancer
Cell Cycle Proteins - metabolism
DNA SEQUENCING
F-Box Proteins - metabolism
F-Box-WD Repeat-Containing Protein 7
FBW7
Gene Expression Regulation, Neoplastic
Humans
Hydroxycholesterols - metabolism
MAMMARY GLANDS
MCF-7 Cells
Myc protein stability
NEOPLASMS
Nuclear Proteins - metabolism
Phosphoprotein Phosphatases - metabolism
PP2A
Protein Phosphatase 2 - metabolism
Proto-Oncogene Proteins c-myc - metabolism
SCP1
STABILITY
TRANSCRIPTION FACTORS
Transcriptional Activation
Ubiquitin-Protein Ligases - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:27-hydroxycholesterol (27-HC), the most abundant metabolite of cholesterol, is a risk factor for breast cancer. It can increase the proliferation of breast cancer cells and promote the metastasis of breast tumours in mouse models. Myc is a critical oncoprotein overexpressed in breast cancer. However, whether 27-HC affects Myc expression has not been reported. In the current study, we aimed to investigate the effects of 27-HC on Myc and the underlying mechanisms in MCF-7 breast cancer cells. Our data demonstrated that 27-HC activated Myc via increasing its protein stability. Three key negative modulators of Myc protein stability, PP2A, SCP1 and FBW7, were suppressed by 27-HC at the transcriptional level. We performed a data-mining analysis of the chromatin immunoprecipitation with next-generation DNA sequencing (ChIP-Seq) data in the ChIPBase, and discovered that a number of putative transcription factors (TFs), including Myc itself, were involved in the transcriptional regulation of PP2A, SCP1 and FBW7. Our results provide a novel mechanistic insight into the activation of Myc by 27-HC via transcriptional repression of PP2A, SCP1 and FBW7 to increase Myc protein stability in breast cancer cells. [Display omitted] •27-Hydroxycholesterol (27-HC) activates Myc via increasing its protein stability.•27-HC inhibits PP2A and SCP1 transcription to block pS62-Myc dephosphorylation.•27-HC suppresses FBW7 transcription to prevent pT58-Myc degradation.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.10.038