Dataset Information

The protein interaction landscape of breast cancer

ABSTRACT: Cancers have been associated with diverse sets of genomic alterations, many of which are rare with uncertain significance. To understand the cellular mechanisms impacted by such alterations in breast invasive carcinoma, we have applied affinity-purification mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer proteins. These networks interconnect and enrich for common and rare cancer mutations; they are also substantially re-wired by mutations, including in TP53 and PIK3CA, and across cancerous and non-cancerous cell contexts. Our analysis identifies a novel AKT-interacting protein, S100A3, which we find activates AKT signaling and is predictive of clinical response to AKT inhibitors. Similarly, UBE2N emerges as a BRCA1 interactor predictive of clinical response to inhibition of PARP. Finally, we 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: PXD019639 | 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
	MCF10A_APMS_MQ.zip	Other
	MCF10A_MCF7_MDA-MB-231_GPA_MQ.zip	Other
	MCF7_APMS_MQ.zip	Other
	MDA-MB-231_APMS_MQ.zip	Other
	MSSampleAnnotatons.xlsx	Xlsx