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

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.
AuthorsKyung-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
JournalCell reports (Cell Rep) Vol. 21 Issue 10 Pg. 2952-2964 (Dec 05 2017) ISSN: 2211-1247 [Electronic] United States
PMID29212038 (Publication Type: Journal Article)
CopyrightCopyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Chemical References
  • BAG2 protein, human
  • Molecular Chaperones
  • Cathepsin B
Topics
  • Apoptosis (genetics, physiology)
  • Breast Neoplasms (metabolism)
  • Cathepsin B (genetics, metabolism)
  • Cell Line, Tumor
  • Female
  • Humans
  • Molecular Chaperones (genetics, metabolism)
  • Triple Negative Breast Neoplasms (genetics, metabolism)

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