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

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

doi:10.1016/j.isci.2023.108399

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

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 WilflingsederMiguel 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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

6 Citations (Scopus)

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.

Original language	English
Pages (from-to)	108399
Journal	iScience
Volume	26
Issue number	12
DOIs	https://doi.org/10.1016/j.isci.2023.108399
Publication status	Published - 15 Dec 2023

Access to Document

10.1016/j.isci.2023.108399

Cite this

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., ... Trajanoski, Z. (2023). Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer. iScience, 26(12), 108399. https://doi.org/10.1016/j.isci.2023.108399

@article{9e7e62f709f3454fbcbe453c4a2ff1b6,

title = "Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer",

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.",

author = "Christina Plattner and Giorgia Lamberti and Peter Blattmann and Alexander Kirchmair and Dietmar Rieder and Zuzana Loncova and Gregor Sturm and Stefan Scheidl and Marieke Ijsselsteijn and Georgios Fotakis and Asma Noureen and Rebecca Lisandrelli and Nina B{\"o}ck and Niloofar Nemati and Anne Krogsdam and Sophia Daum and Francesca Finotello and Antonios Somarakis and Alexander Sch{\"a}fer and Doris Wilflingseder and {Gonzalez Acera}, Miguel and Dietmar {\"O}fner and Huber, {Lukas A} and Hans Clevers and Christoph Becker and Farin, {Henner F} and Greten, {Florian R} and Ruedi Aebersold and {de Miranda}, {Noel F C C} and Zlatko Trajanoski",

note = "{\textcopyright} 2023 The Author(s).",

year = "2023",

month = dec,

day = "15",

doi = "10.1016/j.isci.2023.108399",

language = "English",

volume = "26",

pages = "108399",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "12",

}

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, NFCC & Trajanoski, Z 2023, 'Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer', iScience, vol. 26, no. 12, pp. 108399. https://doi.org/10.1016/j.isci.2023.108399

TY - JOUR

T1 - Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer

AU - Plattner, Christina

AU - Lamberti, Giorgia

AU - Blattmann, Peter

AU - Kirchmair, Alexander

AU - Rieder, Dietmar

AU - Loncova, Zuzana

AU - Sturm, Gregor

AU - Scheidl, Stefan

AU - Ijsselsteijn, Marieke

AU - Fotakis, Georgios

AU - Noureen, Asma

AU - Lisandrelli, Rebecca

AU - Böck, Nina

AU - Nemati, Niloofar

AU - Krogsdam, Anne

AU - Daum, Sophia

AU - Finotello, Francesca

AU - Somarakis, Antonios

AU - Schäfer, Alexander

AU - Wilflingseder, Doris

AU - Gonzalez Acera, Miguel

AU - Öfner, Dietmar

AU - Huber, Lukas A

AU - Clevers, Hans

AU - Becker, Christoph

AU - Farin, Henner F

AU - Greten, Florian R

AU - Aebersold, Ruedi

AU - de Miranda, Noel F C C

AU - Trajanoski, Zlatko

PY - 2023/12/15

Y1 - 2023/12/15

N2 - 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.

AB - 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.

U2 - 10.1016/j.isci.2023.108399

DO - 10.1016/j.isci.2023.108399

M3 - Article

C2 - 38047086

SN - 2589-0042

VL - 26

SP - 108399

JO - iScience

JF - iScience

IS - 12

ER -

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

Abstract

Access to Document

Fingerprint

Cite this