Cathepsin D deficiency in mammary epithelium transiently stalls breast cancer by interference with mTORC1 signaling

Abstract: Cathepsin D (CTSD) is a lysosomal protease and a marker of poor prognosis in breast cancer. However, the cells responsible for this association and the function of CTSD in cancer are still incompletely understood. By using a conditional CTSD knockout mouse crossed to the transgenic MMTV-PyMT breast cancer model we demonstrate that CTSD deficiency in the mammary epithelium, but not in myeloid cells, blocked tumor development in a cell-autonomous manner. We show that lack of CTSD impaired mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling and induced reversible cellular quiescence. In line, CTSD-deficient tumors started to grow with a two-month delay and quiescent Ctsd-/- tumor cells re-started proliferation upon long-term culture. This was accompanied by rewiring of oncogenic gene expression and signaling pathways, while mTORC1 signaling remained permanently disabled in CTSD-deficient cells. Together, these studies reveal a tumor cell-autonomous effect of CTSD deficiency, and establish a pivotal role of this protease in the cellular response to oncogenic stimuli

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature communications. - 11, 1 (2020) , 5133, ISSN: 2041-1723

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Ketterer, Stephanie ; Mitschke, Julia ; Ketscher, Anett ; Schlimpert, Manuel ; Reichardt, Wilfried ; Baeuerle, Natascha ; Hess, Maria Elena ; Metzger, Patrick ; Börries, Melanie ; Peters, Christoph ; Kammerer, Bernd ; Brummer, Tilman ; Steinberg, Florian ; Reinheckel, Thomas

Further information

• DOI: 10.1038/s41467-020-18935-2
• URN: urn:nbn:de:bsz:25-freidok-1679690
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 2025-08-15T07:34:45+0200