Abstract
During tumor development and ongoing metastasis the acquisition of mesenchymal cell traits by epithelial carcinoma cells is achieved through a programmed phenotypic shift called the epithelial-to-mesenchymal transition, EMT. EMT contributes to increased cancer cell motility and invasiveness mainly through invadosomes, the adhesion structures that accompany the mesenchymal migration. The invadosomes and their associated proteases restrict protease activity to areas of the cell in direct contact with the ECM, thus precisely controlling cell invasion. Our data prove that Snail-overexpressing HT-29 cells that imitate the phenotype of colon cancer cells in the early stage of the EMT showed an increase in the expression and pericellular activity of cathepsin B. It appears that the pericellular localization of cathepsin B, also observed in colon and rectum adenocarcinoma tissue samples, plays a key role in its function.
Highlights
Cancer progression is mainly characterized by rapid increases in tumor mass and volume, increased invasiveness, and overall decreases in patient survival rates [1]
The level of matrix metalloproteinases (MMPs)-14 protein was noted altered in HT-29/Snail cells, as we showed in our previous study [9], we investigated the regulation of MMP-2 activity using Furin Inhibitor I [11,74]
We focused on MMP-2 rather than on MMP-9 as MMP-2 is directly activated by MMP-14, whereas MMP-9 is activated by MMP-2 [76,77]
Summary
Cancer progression is mainly characterized by rapid increases in tumor mass and volume (in solid tumors), increased invasiveness, and overall decreases in patient survival rates [1]. Regardless, cancer cells undergo sequential steps to form metastases. To undergo these steps, cancer cells first have to acquire a migratory phenotype and disrupt the tissue architecture, which requires modulation of cell-matrix and cell-cell contacts [3,4,5]. The plasticity of cancer cells is governed by the epithelial-to-mesenchymal transition (EMT) [6]. During the EMT, cells lose their origin markers, polarity, and cell-cell connections and gain mesenchymal-like pro-migratory phenotypes that enable them to cross anatomical boundaries such as the extracellular matrix (ECM) or the basement membrane [7,8]. In tumors EMT contributes to increased cancer cell motility and invasiveness [9,10]. The mesenchymal mode (type) of migration is strongly dependent on GTPase activity, proteolytic degradation of ECM components and adhesion via integrins [11]
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