Dataset Information

Cathepsin B interstitial fluid proteome of murine breast cancers

ABSTRACT: MS-based proteomics study of the interstitial fluid of breast cancer of mice lacking or overexpressing cathepsin B

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

DISEASE(S): Breast Cancer

SUBMITTER: Alejandro Gomez-Auli

LAB HEAD: Oliver Schilling

PROVIDER: PXD002585 | Pride | 2016-03-31

REPOSITORIES: Pride

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Publications

Impact of cathepsin B on the interstitial fluid proteome of murine breast cancers.

Gomez-Auli Alejandro A Hillebrand Larissa Elisabeth LE Biniossek Martin Lothar ML Peters Christoph C Reinheckel Thomas T Schilling Oliver O

Biochimie 20151008

Carcinomas establish a molecular cross talk between malignant tumor cells and the activated non-malignant cells of the tumor stroma. This cell-cell communication in tumor-stroma interaction includes soluble, secreted proteins that act in a paracrine or autocrine manner. Proteases are crucial factors in tumor-stroma interaction by degrading or truncating secreted bioactive proteins. The cysteine protease cathepsin B is frequently overexpressed in several cancer types, including breast cancer. Its ...[more]

PMID: 26455267

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Project description:Single cell transcriptomic analyses (scRNAseq) of hepatocytes and liver endothelial cells (L-EC) have revolutionized the understanding of the spatial architecture of liver structure and function. The spatial alignment of L-EC and hepatocytes is pivotal for liver function in health and disease given that L-EC act as instructive gatekeeper of nearby hepatocytes including the maintenance of liver metabolic zonation in a Wnt-dependent manner. Advancing liver biology beyond the ’transcript-centric’ view of scRNAseq analyses is presently restricted by the limited resolution of proteomics and genome-wide techniques to analyse post-translational modifications. Here, by combining spatial cell sorting methodology with transcriptomic and quantitative proteomic/phospho-proteomic analyses, we established the first functionally and spatially-resolved proteome landscape of the liver endothelium, yielding deep mechanistic insight into zonated vascular signalling mechanisms. Phosphorylation of receptor tyrosine kinases (RTK) was detected preferentially in the central vein area resulting in an atypical enrichment of tyrosine phosphorylation. Prototypic biological validation of the identified strong phosphorylation gradient of the vascular RTK Tie1 by blockade resulted in the rapid peri-central dysregulation of the L-EC transcriptome. Notably, the expression of Wnt9b in L-EC was discovered as Tie receptor controlled with reciprocal regulation by FoxO1 and STAT3 transcription factors. Genetic inactivation of Tie1 in L-EC or antibody blockade resulted in reduced liver regeneration following partial hepatectomy with reduced Wnt ligand and Wnt target gene expression, including Axin2, Sox9, Tbx3 and Lgr5. Taken together, the study has yielded unparalleled insight into the spatial organization of L EC signalling and discovered a vascular Tie-Wnt signalling axis as regulator of liver function. The employed spatial sorting technique followed by phospho-proteomic analysis may be employed as a universally adaptable strategy for the spatial phosphoproteomic analysis of scRNAseq data-defined relevant cellular (sub)-populations.

Dataset Information

Cathepsin B interstitial fluid proteome of murine breast cancers

Publications

Impact of cathepsin B on the interstitial fluid proteome of murine breast cancers.

Similar Datasets

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