Proteomics

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SILAC-Based Quantification of TGFBR2-Dependent Protein Expression in Extracellular Vesicles of Microsatellite Unstable Colorectal Cancers


ABSTRACT: Microsatellite unstable (MSI) colorectal cancers (CRCs) are characterized by Transforming Growth Factor Beta Receptor Type 2 (TGFBR2) deficiency. TGFBR2-deficient CRCs present altered target gene and protein expression. Such cellular alterations modulate the content of CRC-derived extracellular vesicles (EVs). EVs function as couriers of proteins, nucleic acids, and lipids in intercellular communication. At a qualitative level, we have previously shown that TGFBR2 deficiency can cause overall alterations in the EV protein content. To deepen the basic understanding of altered protein dynamics, this work aimed to quantify EV protein signatures in a TGFBR2-dependent manner. Using a SILAC approach for mass spectrometry-based quantification, 48 proteins that appeared to be regulated by cellular TGFBR2 expression were identified in MSI-derived EVs. TGFBR2-primed EVs were enriched in proteasome-associated proteins, whereas TGFBR2 deficiency led to upregulation of EV proteins related to the extracellular matrix and nucleosome. Altogether, the present study emphasizes the general overlap of proteins between EVs and their parental CRC cells and highlights the pathological role of the MSI tumor driver mutation affecting TGFBR2 by altering protein landscapes of EVs. From a clinical perspective, TGFBR2-regulated quantitative differences of protein expression in EVs might nominate novel biomarkers for liquid biopsy-based MSI typing in the future.

INSTRUMENT(S): LTQ Orbitrap, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Fabia Fricke  

LAB HEAD: Jürgen Kopitz

PROVIDER: PXD013980 | Pride | 2019-09-04

REPOSITORIES: Pride

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180731-FF2929_NC1.raw Raw
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Publications

SILAC-Based Quantification of TGFBR2-Regulated Protein Expression in Extracellular Vesicles of Microsatellite Unstable Colorectal Cancers.

Fricke Fabia F   Michalak Malwina M   Warnken Uwe U   Hausser Ingrid I   Schnölzer Martina M   Kopitz Jürgen J   Gebert Johannes J  

International journal of molecular sciences 20190826 17


Microsatellite unstable (MSI) colorectal cancers (CRCs) are characterized by mutational inactivation of <i>Transforming Growth Factor Beta Receptor Type 2</i> (<i>TGFBR2</i>). TGFBR2-deficient CRCs present altered target gene and protein expression. Such cellular alterations modulate the content of CRC-derived extracellular vesicles (EVs). EVs function as couriers of proteins, nucleic acids, and lipids in intercellular communication. At a qualitative level, we have previously shown that TGFBR2 d  ...[more]

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