Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer

Plattner C, Lamberti G, Blattmann P, Kirchmair A, Rieder D, Loncova Z, Sturm G, Scheidl S, Ijsselsteijn M, Fotakis G, Noureen A, Lisandrelli R, Böck N, Nemati N, Krogsdam A, Daum S, Finotello F, Somarakis A, Schäfer A, Wilflingseder D, Gonzalez Acera M, Öfner D, Huber LA, Clevers H, Becker C, Farin HF, Greten FR, Aebersold R, de Miranda NF, Trajanoski Z (2023)

Publication Type: Journal article

Publication year: 2023

Journal

iScience Elsevier

Book Volume: 26

Article Number: 108399

Journal Issue: 12

DOI: 10.1016/j.isci.2023.108399

Abstract

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.

Authors with CRIS profile

Miguel Gonzalez Acera Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie

Involved external institutions

Medizinische Universität Innsbruck AT Austria (AT) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH) Leiden University Medical Center NL Netherlands (NL) Hubrecht Institute NL Netherlands (NL) Georg-Speyer-Haus DE Germany (DE)

How to cite

APA:

Plattner, C., Lamberti, G., Blattmann, P., Kirchmair, A., Rieder, D., Loncova, Z.,... Trajanoski, Z. (2023). Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer. iScience, 26(12). https://dx.doi.org/10.1016/j.isci.2023.108399

MLA:

Plattner, Christina, et al. "Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer." iScience 26.12 (2023).

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