Dataset Information

The protein interaction landscape of breast cancer

ABSTRACT: Cancers have been associated with a diverse array of genomic alterations. To understand such alterations in breast invasive carcinoma at the level of cellular mechanisms, we have applied affinity-purification mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer proteins across three human breast cell lines, providing a resource of context-specific and shared protein-protein interaction networks. These networks interconnect and enrich for common and rare cancer mutations, and are substantially rewired by mutations. Our analysis identifies PIK3CA-interacting proteins which repress AKT signaling, and UBE2N emerges as a BRCA1 interactor predictive of clinical response to PARP inhibition. We also show that Spinophilin interacts with and dephosphorylates BRCA1 to promote DNA double-strand break repair. Thus, cancer protein interaction landscapes provide a framework for recognizing oncogenic drivers and drug vulnerabilities.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Minkyu Kim

LAB HEAD: Nevan Krogan

PROVIDER: PXD025931 | Pride | 2021-11-02

REPOSITORIES: Pride

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A protein interaction landscape of breast cancer.

Kim Minkyu M Park Jisoo J Bouhaddou Mehdi M Kim Kyumin K Rojc Ajda A Modak Maya M Soucheray Margaret M McGregor Michael J MJ O'Leary Patrick P Wolf Denise D Stevenson Erica E Foo Tzeh Keong TK Mitchell Dominique D Herrington Kari A KA Muñoz Denise P DP Tutuncuoglu Beril B Chen Kuei-Ho KH Zheng Fan F Kreisberg Jason F JF Diolaiti Morgan E ME Gordan John D JD Coppé Jean-Philippe JP Swaney Danielle L DL Xia Bing B van 't Veer Laura L Ashworth Alan A Ideker Trey T Krogan Nevan J NJ

Science (New York, N.Y.) 20211001 6563

Cancers have been associated with a diverse array of genomic alterations. To help mechanistically understand such alterations in breast-invasive carcinoma, we applied affinity purification–mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer (BC) proteins, with and without relevant mutations, across three human breast cell lines. These networks identify cancer-specific protein-protein interactions (PPIs), interconnected and enriche ...[more]

PMID: 34591612

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			Action	DRS
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	MDA-MB-231_USP28_Ub_MQ.zip	Other
	MS_PTM_Sample_Annotatons.xlsx	Xlsx
	lu0103813.raw	Raw
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