The secreted inhibitor of invasive cell growth CREG1 is negatively regulated by cathepsin proteases.

The secreted inhibitor of invasive cell growth CREG1 is negatively regulated by cathepsin proteases. Cell Mol Life Sci. 2020 May 08;: Authors: Gomez-Auli A, Hillebrand LE, Christen D, Günther SC, Biniossek ML, Peters C, Schilling O, Reinheckel T Abstract Previous clinical and experimental evidence strongly supports a breast cancer-promoting function of the lysosomal protease cathepsin B. However, the cathepsin B-dependent molecular pathways are not completely understood. Here, we studied the cathepsin-mediated secretome changes in the context of the MMTV-PyMT breast cancer mouse model. Employing the cell-conditioned media from tumor-macrophage co-cultures, as well as tumor interstitial fluid obtained by a novel strategy from PyMT mice with differential cathepsin B expression, we identified an important proteolytic and lysosomal signature, highlighting the importance of this organelle and these enzymes in the tumor micro-environment. The Cellular Repressor of E1A Stimulated Genes 1 (CREG1), a secreted endolysosomal glycoprotein, displayed reduced abundance upon over-expression of cathepsin B as well as increased abundance upon cathepsin B deletion or inhibition. Moreover, it was cleaved by cathepsin B in vitro. CREG1 reportedly could act as tumor suppressor. We show that treatment of PyMT tumor cells with recombinant CREG1 reduced proliferation, migration, and invasion; whereas, the opposite was observed with reduced CREG1 expression...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research