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| Status |
Public on Oct 23, 2018 |
| Title |
SMAD2 binding regions in estrogen receptor-positive breast cancer cell line, T47D |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Inhibitors for cyclin-dependent kinase (CDK) 4 and CDK6 have been established as effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although the CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we have focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor Palbociclib and Activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Mechanistically, Palbociclib enhanced SMAD2 binding to the genome through inhibiting linker phosphorylation of the SMAD2 protein by CDK4/6. Comparison of the SMAD2 ChIP-seq data of T47D with those of a triple-negative breast cancer cell line Hs578T indicated that Palbociclib augments different SMAD2-mediated program defined based on types of cells, and enhances SMAD2 binding to the target regions on the genome without affecting its binding pattern. Collectively, the CDK4/6 inhibitor facilitates the cytostatic effects of Activin-SMAD2, while it also enhances its tumor promoting effects depending on types of breast cancer.
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| Overall design |
SMAD2 ChIP-seq analysis was performed in estrogen receptor-positive breast cancer after Activin A with/without Palbociclib treatment
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| Contributor(s) |
Harada M, Morikawa M, Ozawa T, Tamura Y, Miyazono K, Koinuma D |
| Citation(s) |
30343527 |
| Submission date |
Jul 23, 2018 |
| Last update date |
Mar 01, 2019 |
| Contact name |
Daizo Koinuma |
| E-mail(s) |
d-koinuma@umin.ac.jp
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| Organization name |
University of Tokyo
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| Department |
Pathology
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| Street address |
Hongo 7-3-1, Bunkyo-ku
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| City |
Tokyo |
| ZIP/Postal code |
113-0033 |
| Country |
Japan |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (5)
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| GSM3301947 |
T47D, SMAD2 binding region after ActA stimulation, rep1 |
| GSM3301948 |
T47D, SMAD2 binding region after ActA stimulation and Palbo treatment, rep1 |
| GSM3301949 |
T47D, SMAD2 binding region after ActA stimulation, rep2 |
| GSM3301950 |
T47D, SMAD2 binding region after ActA stimulation and Palbo treatment, rep2 |
| GSM3301951 |
T47D, input |
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| This SubSeries is part of SuperSeries: |
| GSE117502 |
SMAD2 binding regions in breast cancer cell line and RNA-seq transcriptome analyses in T47D |
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| Relations |
| BioProject |
PRJNA482344 |
| SRA |
SRP154853 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE117495_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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