Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting the vulnerability of RB tumor suppressor loss in triple negative breast cancer

ABSTRACT: Targeting the vulnerability of RB tumor suppressor loss in triple negative breast cancer

PROVIDER: PRJNA428502 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6493560.fastq.gz	Fastqsanger.gz
	SRR6493561.fastq.gz	Fastqsanger.gz
	SRR6493562.fastq.gz	Fastqsanger.gz
	SRR6493563.fastq.gz	Fastqsanger.gz
	SRR6493564.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 13

Similar Datasets

Targeting the vulnerability of RB tumor suppressor loss in triple negative breast cancer

Project description:Approximately 30% of TNBCs exhibit loss of function of the RB tumor suppressor. The study used RNA sequencing to profile RB-proficient and RB-deficient TNBC cases that were defined based on immunostaining for RB and p16ink4a. The analyses revealed that RB-deficient TNBC cases express elevated levels of DNA replication and mitotic genes that could serve as the basis for increased sensitivity to drugs targeting cell cycle checkpoints.

2018-01-05 | GSE108757 | GEO

Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.

Project description:Approximately 30% of triple-negative breast cancers (TNBCs) exhibit functional loss of the RB tumor suppressor, suggesting a target for precision intervention. Here, we use drug screens to identify agents specifically antagonized by the retinoblastoma tumor suppressor (RB) using CDK4/6 inhibitors. A number of candidate RB-synthetic lethal small molecules were identified, including anti-helmenthics, chemotherapeutic agents, and small-molecule inhibitors targeting DNA-damage checkpoints (e.g., CHK) and chromosome segregation (e.g., PLK1). Counter-screens using isogenic TNBC tumor cell lines and cell panels with varying endogenous RB statuses confirmed that therapeutic effects were robust and selective for RB loss of function. By analyzing TNBC clinical specimens, RB-deficient tumors were found to express high levels of CHK1 and PLK1. Loss of RB specifically resulted in loss of checkpoint functions governing DNA replication, yielding increased drug sensitivity. Xenograft models demonstrated RB-selective efficacy of CHK inhibitors. This study supports the possibility of selectively targeting RB loss in the treatment of TNBC.

| S-EPMC5967622 | biostudies-literature

Targeting EZH2 increases the vulnerability of triple-negative breast cancer

Project description:Targeting EZH2 increases the vulnerability of triple-negative breast cancer

| PRJNA445854 | ENA

RB tumor suppressor promotes cancer immunity through downregulating PD-L1 expression

Project description:Aberrant expression of immune checkpoint protein programmed death ligand-1 (PD-L1) promotes immune tolerance in cancer. RB is a tumor suppressor known to regulate the cell cycle, DNA damage response, and differentiation. Here, we demonstrate transient knockdown or homozygous deletion of RB markedly induces PD-L1 mRNA expression. RB binds to NFκB protein p65 and serine-249/threonine-252 (S249/T252) phosphorylation of RB is important for its interaction with p65 and suppression of PD-L1 expression. RNA-seq analysis identifies a subset of NFκB pathway genes including PD-L1 are selectively upregulated by RB knockdown. S249/T252-phosphorylated RB inversely correlates with PD-L1 expression in patient samples. Expression of a RB-derived S249/T252 phospho-mimicking peptide blocks radiation-induced PD-L1 expression and increases the anti-cancer efficacy of radiation in mice. Our findings reveal a previously unappreciated tumor suppressor function of hyperphosphorylated RB in inhibition of NFκB activity and PD-L1 expression, suggesting this regulatory module can be exploited to overcome cancer immune evasion.

2018-11-19 | GSE109724 | GEO

MYC-Alarmin Axis as a Novel Therapeutic Vulnerability in Triple Negative Myeloproliferative Neoplasms

Project description:Despite advances in our understanding of the underlying genetic abnormalities in myelofibrosis (MF) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly in triple negative MF patients who lack mutations in the JAK2 kinase pathway. Here we report that MYC copy number gain (e.g., trisomy 8) is frequently identified in triple negative MF where MF development and progression rely on MYC-directed activation of S100A9, a Danger Associated Molecular Pattern (DAMP) protein that plays pivotal roles in inflammation. Notably, MYC-S100A9 axis underlies complex network of inflammatory signaling that involves various hematopoietic cell types in the bone marrow microenvironment. Accordingly, small molecules targeting the MYC-S100A9 pathway effectively ameliorated the MF phenotypes, highlighting MYC-alarmin axis as a novel therapeutic vulnerability in a subgroup of MF patients.

2024-04-29 | GSE240963 | GEO

Localization of the Rb tumor suppressor in MEFs during reprogramming to iPS and the consequence of Rb loss on the transcriptional profile and histone landscape in these cells

Project description:The reprogramming of differentiated cells to an embryonic stem cell-like state provides a powerful system to explore fundamental mechanisms of development, including how mammalian cells establish and maintain pluripotency and long-term self-renewal capability. Based on the similarities between embryonic stem cells and cancer cells, we investigated the potential role of the retinoblastoma tumor suppressor and cell cycle regulator RB in the reprogramming of fibroblasts into induced pluripotent stem cells (iPS cells). Herein we demonstrate that loss of RB function leads to both an acceleration of the reprogramming process and the generation of more iPS clones from fibroblasts. This effect is largely due to a restrictive role for RB at the early stages of reprogramming. Surprisingly, however, RB inactivation does not enhance the formation of iPS clones by accelerating the proliferation of cells undergoing reprogramming. Rather, a genome-wide investigation of RB targets indicates that RB binds to regulatory regions of pluripotency genes such as Sox2 and Oct4 and contributes to their full repression in differentiated cells. This effect correlates with the maintenance of a repressive chromatin structure at these loci. Accordingly, Rb-deficient fibroblasts can be reprogrammed into iPS cells even in the absence of exogenous Sox2, which is normally required to initiate reprogramming from fibroblasts. These experiments identify a novel barrier in the reprogramming process, mainly the repression of certain pluripotency genes such as Sox2 by RB, which provides a new link between tumor suppressor mechanisms and cellular reprogramming. RNAseq from MEFs with 2 biological replicates (save CP), Rb ChIPseq from MEFs with 2 biological replicates, Histone H3 modification ChIPseq from MEFs with 1 biological replicate

2014-11-13 | E-GEOD-40594 | biostudies-arrayexpress

Localization of the Rb tumor suppressor in MEFs during reprogramming to iPS and the consequence of Rb loss on the transcriptional profile and histone landscape in these cells

2014-11-13 | GSE40594 | GEO

MYC-Alarmin Axis as a Novel Therapeutic Vulnerability in Triple Negative Myeloproliferative Neoplasms

Project description:MYC-Alarmin Axis as a Novel Therapeutic Vulnerability in Triple Negative Myeloproliferative Neoplasms

| PRJNA1005951 | ENA

A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer

Project description:Paclitaxel -resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly. Genetic or pharmacologic inhibition of PRMT5 alters RNA splicing, particularly intron retention of Aurora kinases B (AURKB), leading to a decrease in protein expression, and finally results in selective mitosis catastrophe in paclitaxel-resistant cells. These findings are fully recapitulated in a patient derived xenograft (PDX) model generated from a paclitaxel-resistant TNBC patient, providing the rationale for targeting PRMTs in paclitaxel-resistant TNBC.

2024-06-21 | GSE264630 | GEO

RB tumor suppressor promotes cancer immunity through downregulating PD-L1 expression

Project description:RB tumor suppressor promotes cancer immunity through downregulating PD-L1 expression

| PRJNA431800 | ENA