Co-chaperone BAG2 Determines the Pro-oncogenic Role of Cathepsin B in Triple-Negative Breast Cancer Cells
In: Cell Reports, Jg. 21 (2017-12-05), Heft 10, S. 2952-2964
Online
serialPeriodical
Zugriff:
Triple-negative breast cancer (TNBC) is considered incurable with currently available treatments, highlighting the need for therapeutic targets and predictive biomarkers. Here, we report a unique role for Bcl-2-associated athanogene 2 (BAG2), which is significantly overexpressed in TNBC, in regulating the dual functions of cathepsin B as either a pro- or anti-oncogenic enzyme. Silencing BAG2 suppresses tumorigenesis and lung metastasis and induces apoptosis by increasing the intracellular mature form of cathepsin B, whereas BAG2 expression induces metastasis by blocking the auto-cleavage processing of pro-cathepsin B via interaction with the propeptide region. BAG2 regulates pro-cathepsin B/annexin II complex formation and facilitates the trafficking of pro-cathespin-B-containing TGN38-positive vesicles toward the cell periphery, leading to the secretion of pro-cathepsin B, which induces metastasis. Collectively, our results uncover BAG2 as a regulator of the oncogenic function of pro-cathepsin B and a potential diagnostic and therapeutic target that may reduce the burden of metastatic breast cancer.
Titel: |
Co-chaperone BAG2 Determines the Pro-oncogenic Role of Cathepsin B in Triple-Negative Breast Cancer Cells
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Autor/in / Beteiligte Person: | Yang, Kyung-Min ; Bae, Eunjin ; Ahn, Sung Gwe ; Pang, Kyoungwha ; Park, Yuna ; Park, Jinah ; Lee, Jihee ; Ooshima, Akira ; Park, Bora ; Kim, Junil ; Jung, Yunshin ; Takahashi, Satoru ; Jeong, Joon ; Park, Seok Hee ; Kim, Seong-Jin |
Link: | |
Zeitschrift: | Cell Reports, Jg. 21 (2017-12-05), Heft 10, S. 2952-2964 |
Veröffentlichung: | 2017 |
Medientyp: | serialPeriodical |
ISSN: | 2211-1247 (print) |
DOI: | 10.1016/j.celrep.2017.11.026 |
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