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Co-chaperone BAG2 Determines the Pro-oncogenic Role of Cathepsin B in Triple-Negative Breast Cancer Cells.

Authors
 Kyung-Min Yang  ;  Eunjin Bae  ;  Sung Gwe Ahn  ;  Kyoungwha Pang  ;  Yuna Park  ;  Jinah Park  ;  Jihee Lee  ;  Akira Ooshima  ;  Bora Park  ;  Junil Kim  ;  Yunshin Jung  ;  Satoru Takahashi  ;  Joon Jeong  ;  Seok Hee Park  ;  Seong-Jin Kim 
Citation
 Cell Reports, Vol.21(10) : 2952-2964, 2017 
Journal Title
 Cell Reports 
Issue Date
2017
Keywords
BAG2 ; TGN38 ; TNBC ; breast cancer ; cathepsin B ; metastasis ; tumorigenesis
Abstract
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/161548
DOI
10.1016/j.celrep.2017.11.026
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
안성귀(Ahn, Sung Gwe) ; 정준(Jeong, Joon)
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