2024-03-28T08:42:45Z
https://tsukuba.repo.nii.ac.jp/oai
oai:tsukuba.repo.nii.ac.jp:00044602
2023-02-09T02:15:26Z
2780:544
3:62:5298:5294
Co-chaperone BAG2 Determines the Pro-oncogenic Role of Cathepsin B in Triple-Negative Breast Cancer Cells
Yang, Kyung-Min
Bae, Eunjin
Ahn, Sung Gwe
Pang, Kyoungwha
Park, Yuna
Park, Jinah
Lee, Jihee
Ooshima, Akira
Park, Bora
Kim, Junil
Jung, Yunshin
高橋, 智
タカハシ, サトル
TAKAHASHI, Satoru
Jeong, Joon
Park, Seok Hee
Kim, Seong-Jin
open access
(c) 2017 The Author(s).
This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ).
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.
Cell Press
2017-12
eng
journal article
VoR
http://hdl.handle.net/2241/00149875
https://tsukuba.repo.nii.ac.jp/records/44602
29212038
https://doi.org/10.1016/j.celrep.2017.11.026
2211-1247
Cell Reports
21
10
2952
2964
https://tsukuba.repo.nii.ac.jp/record/44602/files/CR_21-10.pdf
application/pdf
5.7 MB
2018-01-04