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ChIP-sequencing of ZEB1 in triple negative breast cancer cell line Hs578T

ABSTRACT: ChIP-sequencing of ZEB1 in triple negative breast cancer cell line Hs578T

PROVIDER: PRJEB17984 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR1735900.fastq.gz	Fastqsanger.gz
	ERR1735901.fastq.gz	Fastqsanger.gz
	ERR1735898.fastq.gz	Fastqsanger.gz
	ERR1735899.fastq.gz	Fastqsanger.gz

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ChIP-sequencing of ZEB1 in triple negative breast cancer cell line Hs578T

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Project description: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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