FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2944298541> ?p ?o ?g. }

• W2944298541 abstract "A key unanswered question in cancer genetics is how different mutations, dispersed across a multitude of genes, elicit similar pathology and patient outcomes. The answer may lie in understanding the molecular networks and protein complexes (i.e. signaling pathways, chromatin architecture, etc) in cancer and mapping mutated genes into the complexes and pathways in which they function. Determining how systematic interaction networks are wired in cancer cells and how different mutations perturb these networks will guide the search for new cancer genes and provide a platform for integrating patient data to make biological and clinical predictions more accurate. The goal of this study is to uncover the comprehensive protein-protein interaction networks and pathways in various breast cancer subtypes to better understand how mutated cancer genes and genomes hijack and re-wire pathways and complexes during the course of breast tumorigenesis. Here we catalog protein-protein interactions for 40 genes recurrently mutated in breast cancer, using affinity purification and mass spectrometry. To identify co-associated proteins, cDNA clones expressing each protein were tagged with 3xFLAG at either N or C-terminus and introduced into MCF10A (non-tumorigenic “healthy” control), MCF7 (luminal A subtype), and MDA-MB-231 (claudin-low) cells using doxycycline-inducible lentiviral vectors. For proteins with prevalent pathogenic mutations (e.g. PIK3CA-H1047R, BRCA1-C61G), mutant cDNA clones were also analyzed in parallel. Our interaction network reveals subtype and mutation-specific protein-protein interactions, many of which are not previously reported. Given that genes encoding components of a protein complex or a biological pathway often share similar phenotype upon genetic perturbation, we genetically knocked out genes interacting with DNA damage response (DDR) proteins using CRISPR/Cas9, and found multiple novel interacting genes whose knockout results in significant PARPi (olaparib) and/or cisplatin sensitivity. This result not only functionally validates the physical protein interactions, but also demonstrates that our interactome mapping approach can helps identify newdruggable vulnerabilities in cancer cells. We anticipate the breast cancer interactome study will uncover aberrant pathways and protein complexes uniquely operating in breast cancer cells, and thus pinpoint proteins that may potentially serve as distinct biomarkers or therapeutic targets for tumors having the same or similar subtypes and/or genomic mutations. Citation Format: Kim M, Kim K, Tutuncuoglu B, Soucheray M, Swaney D, Zheng F, Park J, O9Leary P, Coppe J-P, van 9t Veer L, Ashworth A, Ideker T, Krogan N. Analyzing the physical and functional protein interaction landscape of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-06-01." @default.
• W2944298541 created "2019-05-16" @default.
• W2944298541 creator A5005930950 @default.
• W2944298541 creator A5025723984 @default.
• W2944298541 creator A5026080576 @default.
• W2944298541 creator A5045412635 @default.
• W2944298541 creator A5045559304 @default.
• W2944298541 creator A5047913350 @default.
• W2944298541 creator A5050814288 @default.
• W2944298541 creator A5058973407 @default.
• W2944298541 creator A5059175082 @default.
• W2944298541 creator A5067852069 @default.
• W2944298541 creator A5071139795 @default.
• W2944298541 creator A5087550248 @default.
• W2944298541 creator A5089373684 @default.
• W2944298541 date "2019-02-15" @default.
• W2944298541 modified "2023-09-27" @default.
• W2944298541 title "Abstract P6-06-01: Analyzing the physical and functional protein interaction landscape of breast cancer" @default.
• W2944298541 doi "https://doi.org/10.1158/1538-7445.sabcs18-p6-06-01" @default.
• W2944298541 hasPublicationYear "2019" @default.
• W2944298541 type Work @default.
• W2944298541 sameAs 2944298541 @default.
• W2944298541 citedByCount "0" @default.
• W2944298541 crossrefType "proceedings-article" @default.
• W2944298541 hasAuthorship W2944298541A5005930950 @default.
• W2944298541 hasAuthorship W2944298541A5025723984 @default.
• W2944298541 hasAuthorship W2944298541A5026080576 @default.
• W2944298541 hasAuthorship W2944298541A5045412635 @default.
• W2944298541 hasAuthorship W2944298541A5045559304 @default.
• W2944298541 hasAuthorship W2944298541A5047913350 @default.
• W2944298541 hasAuthorship W2944298541A5050814288 @default.
• W2944298541 hasAuthorship W2944298541A5058973407 @default.
• W2944298541 hasAuthorship W2944298541A5059175082 @default.
• W2944298541 hasAuthorship W2944298541A5067852069 @default.
• W2944298541 hasAuthorship W2944298541A5071139795 @default.
• W2944298541 hasAuthorship W2944298541A5087550248 @default.
• W2944298541 hasAuthorship W2944298541A5089373684 @default.
• W2944298541 hasConcept C104317684 @default.
• W2944298541 hasConcept C11804247 @default.
• W2944298541 hasConcept C121608353 @default.
• W2944298541 hasConcept C143065580 @default.
• W2944298541 hasConcept C501734568 @default.
• W2944298541 hasConcept C502942594 @default.
• W2944298541 hasConcept C530470458 @default.
• W2944298541 hasConcept C54355233 @default.
• W2944298541 hasConcept C55105296 @default.
• W2944298541 hasConcept C555283112 @default.
• W2944298541 hasConcept C70721500 @default.
• W2944298541 hasConcept C83640560 @default.
• W2944298541 hasConcept C86803240 @default.
• W2944298541 hasConceptScore W2944298541C104317684 @default.
• W2944298541 hasConceptScore W2944298541C11804247 @default.
• W2944298541 hasConceptScore W2944298541C121608353 @default.
• W2944298541 hasConceptScore W2944298541C143065580 @default.
• W2944298541 hasConceptScore W2944298541C501734568 @default.
• W2944298541 hasConceptScore W2944298541C502942594 @default.
• W2944298541 hasConceptScore W2944298541C530470458 @default.
• W2944298541 hasConceptScore W2944298541C54355233 @default.
• W2944298541 hasConceptScore W2944298541C55105296 @default.
• W2944298541 hasConceptScore W2944298541C555283112 @default.
• W2944298541 hasConceptScore W2944298541C70721500 @default.
• W2944298541 hasConceptScore W2944298541C83640560 @default.
• W2944298541 hasConceptScore W2944298541C86803240 @default.
• W2944298541 hasLocation W29442985411 @default.
• W2944298541 hasOpenAccess W2944298541 @default.
• W2944298541 hasPrimaryLocation W29442985411 @default.
• W2944298541 hasRelatedWork W1503031859 @default.
• W2944298541 hasRelatedWork W2017409194 @default.
• W2944298541 hasRelatedWork W2060908722 @default.
• W2944298541 hasRelatedWork W2105800735 @default.
• W2944298541 hasRelatedWork W2128058093 @default.
• W2944298541 hasRelatedWork W2203149581 @default.
• W2944298541 hasRelatedWork W2269192044 @default.
• W2944298541 hasRelatedWork W2281699589 @default.
• W2944298541 hasRelatedWork W2293900604 @default.
• W2944298541 hasRelatedWork W2315582552 @default.
• W2944298541 hasRelatedWork W2408027290 @default.
• W2944298541 hasRelatedWork W2408035017 @default.
• W2944298541 hasRelatedWork W2480113753 @default.
• W2944298541 hasRelatedWork W2567411016 @default.
• W2944298541 hasRelatedWork W2608769745 @default.
• W2944298541 hasRelatedWork W2697722282 @default.
• W2944298541 hasRelatedWork W2771289428 @default.
• W2944298541 hasRelatedWork W2884516991 @default.
• W2944298541 hasRelatedWork W2885104529 @default.
• W2944298541 hasRelatedWork W2955559771 @default.
• W2944298541 isParatext "false" @default.
• W2944298541 isRetracted "false" @default.
• W2944298541 magId "2944298541" @default.
• W2944298541 workType "article" @default.