Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer
Summary: Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology—a strategy that is based on perturbing primary tumor cells from cancer patients—could provide a road forward to personalize treatment. We extend...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223024768 |
| _version_ | 1827582104652742656 |
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| author | Christina Plattner Giorgia Lamberti Peter Blattmann Alexander Kirchmair Dietmar Rieder Zuzana Loncova Gregor Sturm Stefan Scheidl Marieke Ijsselsteijn Georgios Fotakis Asma Noureen Rebecca Lisandrelli Nina Böck Niloofar Nemati Anne Krogsdam Sophia Daum Francesca Finotello Antonios Somarakis Alexander Schäfer Doris Wilflingseder Miguel Gonzalez Acera Dietmar Öfner Lukas A. Huber Hans Clevers Christoph Becker Henner F. Farin Florian R. Greten Ruedi Aebersold Noel F.C.C. de Miranda Zlatko Trajanoski |
| author_facet | Christina Plattner Giorgia Lamberti Peter Blattmann Alexander Kirchmair Dietmar Rieder Zuzana Loncova Gregor Sturm Stefan Scheidl Marieke Ijsselsteijn Georgios Fotakis Asma Noureen Rebecca Lisandrelli Nina Böck Niloofar Nemati Anne Krogsdam Sophia Daum Francesca Finotello Antonios Somarakis Alexander Schäfer Doris Wilflingseder Miguel Gonzalez Acera Dietmar Öfner Lukas A. Huber Hans Clevers Christoph Becker Henner F. Farin Florian R. Greten Ruedi Aebersold Noel F.C.C. de Miranda Zlatko Trajanoski |
| author_sort | Christina Plattner |
| collection | DOAJ |
| description | Summary: Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology—a strategy that is based on perturbing primary tumor cells from cancer patients—could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cytometry-based profiling of the primary tumors, we characterize the tumor microenvironment (TME) and determine spatial heterocellular crosstalk and tumor-immune cell interactions. Collectively, we provide a framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno-) oncology in CRC. |
| first_indexed | 2024-03-08T22:45:45Z |
| format | Article |
| id | doaj.art-e7b86d875dee498688afb5b6da71b4a9 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:45Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-e7b86d875dee498688afb5b6da71b4a92023-12-17T06:40:38ZengElsevieriScience2589-00422023-12-012612108399Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancerChristina Plattner0Giorgia Lamberti1Peter Blattmann2Alexander Kirchmair3Dietmar Rieder4Zuzana Loncova5Gregor Sturm6Stefan Scheidl7Marieke Ijsselsteijn8Georgios Fotakis9Asma Noureen10Rebecca Lisandrelli11Nina Böck12Niloofar Nemati13Anne Krogsdam14Sophia Daum15Francesca Finotello16Antonios Somarakis17Alexander Schäfer18Doris Wilflingseder19Miguel Gonzalez Acera20Dietmar Öfner21Lukas A. Huber22Hans Clevers23Christoph Becker24Henner F. Farin25Florian R. Greten26Ruedi Aebersold27Noel F.C.C. de Miranda28Zlatko Trajanoski29Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8092 Zurich, SwitzerlandBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Radiology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8092 Zurich, SwitzerlandInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Medicine 1, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054 Erlangen, GermanyDepartment of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, AustriaBiocenter, Institute of Cell Biology, Medical University of Innsbruck, 6020 Innsbruck, AustriaHubrecht Institute, 3584 CT Utrecht, the NetherlandsDepartment of Medicine 1, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054 Erlangen, GermanyInstitute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt am Main, Germany; Frankfurt Cancer Institute, Goethe University, 60596 Frankfurt am Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, a partnership with DKFZ Heidelberg, Frankfurt/Mainz, GermanyInstitute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt am Main, Germany; Frankfurt Cancer Institute, Goethe University, 60596 Frankfurt am Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, a partnership with DKFZ Heidelberg, Frankfurt/Mainz, GermanyDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8092 Zurich, SwitzerlandDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsBiocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, Austria; Corresponding authorSummary: Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology—a strategy that is based on perturbing primary tumor cells from cancer patients—could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cytometry-based profiling of the primary tumors, we characterize the tumor microenvironment (TME) and determine spatial heterocellular crosstalk and tumor-immune cell interactions. Collectively, we provide a framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno-) oncology in CRC.http://www.sciencedirect.com/science/article/pii/S2589004223024768Cancer systems biologyCancerProteomics |
| spellingShingle | Christina Plattner Giorgia Lamberti Peter Blattmann Alexander Kirchmair Dietmar Rieder Zuzana Loncova Gregor Sturm Stefan Scheidl Marieke Ijsselsteijn Georgios Fotakis Asma Noureen Rebecca Lisandrelli Nina Böck Niloofar Nemati Anne Krogsdam Sophia Daum Francesca Finotello Antonios Somarakis Alexander Schäfer Doris Wilflingseder Miguel Gonzalez Acera Dietmar Öfner Lukas A. Huber Hans Clevers Christoph Becker Henner F. Farin Florian R. Greten Ruedi Aebersold Noel F.C.C. de Miranda Zlatko Trajanoski Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer iScience Cancer systems biology Cancer Proteomics |
| title | Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer |
| title_full | Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer |
| title_fullStr | Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer |
| title_full_unstemmed | Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer |
| title_short | Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer |
| title_sort | functional and spatial proteomics profiling reveals intra and intercellular signaling crosstalk in colorectal cancer |
| topic | Cancer systems biology Cancer Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223024768 |
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