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Proteomic profiling...
Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling
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- De Marchi, Tommaso (author)
- Lund University,Lunds universitet,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breast cancer Proteogenomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Lai, Chun-Fui (author)
- Imperial College London
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- Simmons, Georgia M (author)
- Imperial College London
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- Goldsbrough, Isabella (author)
- Imperial College London
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- Harrod, Alison (author)
- Imperial College London
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- Lam, Thai (author)
- Lund University
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- Buluwela, Lakjaya (author)
- Imperial College London
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- Kjellström, Sven (author)
- Lund University,Lunds universitet,BioMS,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Brueffer, Christian (author)
- Lund University,Lunds universitet,Translational Oncogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Saal, Lao H (author)
- Lund University,Lunds universitet,Translational Oncogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Malmström, Johan (author)
- Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,BioMS,LTH profilområde: Teknik för hälsa,LTH profilområden,Lunds Tekniska Högskola,Lund University Research Groups,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH
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- Ali, Simak (author)
- Imperial College London
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- Niméus, Emma (author)
- Lund University,Lunds universitet,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breast cancer Proteogenomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Scientific Reports. - 2045-2322. ; 14, s. 1-16
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Abstract
Subject headings
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- Three quarters of all breast cancers express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancer, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and without direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and mTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells. Our study is the first proteome-centric characterization of ESR1 mutant models, out of which we confirm estrogen independence of ER mutants and reveal the enrichment of immune signaling pathways at the proteomic level.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Humans
- Female
- Cyclin-Dependent Kinases/genetics
- Proteome/genetics
- Proteomics
- Estrogen Receptor alpha/genetics
- Breast Neoplasms/pathology
- Mutation
- Estrogens
- Receptors, Estrogen/genetics
- Phosphoproteins/genetics
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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De Marchi, Tomma ...
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Lai, Chun-Fui
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Simmons, Georgia ...
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Goldsbrough, Isa ...
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Harrod, Alison
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Lam, Thai
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show more...
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Buluwela, Lakjay ...
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Kjellström, Sven
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Brueffer, Christ ...
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Saal, Lao H
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Malmström, Johan
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Ali, Simak
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Niméus, Emma
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Scientific Repor ...
- By the university
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Lund University