Lysosomal protein turnover contributes to the acquisition of TGFβ-1 induced invasive properties of mammary cancer cells

Molecular Cancer
Ursula KernThomas Reinheckel

Abstract

Normal epithelial cells and carcinoma cells can acquire invasiveness by epithelial-to-mesenchymal transition (EMT), a process of considerable cellular remodeling. The endosomal/lysosomal compartment is a principal site of intracellular protein degradation. Lysosomal cathepsin proteases are secreted during cancer progression. The established pro-metastatic role of specific cysteine cathepsins has until now been ascribed to their contribution to extracellular matrix remodeling. We hypothesized that cysteine cathepsins affect transforming growth factor β-1 (TGFβ-1)-induced EMT of normal and malignant mammary epithelial cells. The role of lysosomal proteolysis in TGFβ-1-induced EMT and invasion was investigated in a normal and a novel malignant murine mammary epithelial cell line. The contribution of cysteine cathepsins was determined by addition of the general cysteine cathepsin inhibitor E64d. Hallmarks of EMT were analyzed by molecular- and cell-biologic analyses including real-time cell migration/invasion assays. A quantitative proteome comparison using stable isotopic labeling with amino acids in culture (SILAC) showed the effect of E64d on TGFβ-1 induced proteome changes. Lysosomal patterning and junctional adhesion molecule ...Continue Reading

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Citations

Nov 26, 2015·Nature Reviews. Cancer·Oakley C Olson, Johanna A Joyce
Nov 1, 2017·The Journal of Pathology·Hendrika M DuivenvoordenBelinda S Parker
Sep 5, 2019·Cancer Metastasis Reviews·Julia MitschkeThomas Reinheckel
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Aug 9, 2018·Clinical Proteomics·Vanessa DrendelOliver Schilling
May 10, 2020·Cellular and Molecular Life Sciences : CMLS·Alejandro Gomez-AuliThomas Reinheckel
Dec 30, 2021·Biomedit︠s︡inskai︠a︡ khimii︠a︡·T A GureevaN I Solovyova

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Methods Mentioned

BETA
transgenic
flow cytometry
FCS
protein assay
Assay
FACS

Software Mentioned

MaxQuant
STRING
Origin®
STRING ( Search Tool for the Retrieval of interacting Genes )
xCelligence
FlowJo

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