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SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149371 | GEO | 2020/04/27

REPOSITORIES: GEO

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SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells II

Project description:Oncoproteins such as the BRAFV600E kinase entrust cancer cells with malignant properties, but they also create unique vulnerabilies. Therapeutic targeting of the BRAFV600E-driven cytoplasmic signaling network has proven ineffective, since patients regularly relapse with reactivation of the targeted signaling pathways. Here, we identified the nuclear protein SFPQ to be synthetically lethal with BRAFV600E in a loss-of-function shRNA screen. SFPQ depletion decreased proliferation and induced apoptosis in BRAFV600E-driven colorectal and melanoma cells, and reduced tumor growth in xenografts. Mechanistically, SFPQ loss in BRAF-mutant cancer cells triggered the Chk1-dependent replication checkpoint, resulting in replication stress in the absence of overt DNA damage. Affected cells stalled in S-Phase with hallmark signs of impaired replication factories. Induction of BRAFV600E and concomitant loss of SFPQ sensitized cells to a combination of DNA replication checkpoint inhibitors and chemically induced replication stress, pointing towards future therapeutic approaches exploiting nuclear vulnerabilities induced by BRAFV600E.

2020-04-27 | GSE149370 | GEO

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells I

2019-12-31 | GSE116631 | GEO

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells

Project description:SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells

| PRJNA628515 | ENA

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells II

Project description:SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells II

| PRJNA628517 | ENA

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells I

Project description:SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells I

| PRJNA479751 | ENA

Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-02-12 | E-GEOD-55032 | biostudies-arrayexpress

AR and c-Myb depletion effects in prostate cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-28 | E-GEOD-49287 | biostudies-arrayexpress

Identification of miRNAs that regulate Colorectal Cancer Metastasis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-01-15 | E-GEOD-56320 | biostudies-arrayexpress

Stromal contribution to expression signatures of colorectal cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-01 | E-GEOD-56710 | biostudies-arrayexpress

UHRF1 depletion and HDAC inhibition synergistically reactivate epigenetically silenced genes in colorectal cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-05-21 | GSE106439 | GEO

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