C-terminal HSP90 inhibitor L80 elicits anti-metastatic effects in triple-negative breast cancer via STAT3 inhibition
- Authors
- Cho, Tae-Min; Kim, Ji Young; Kim, Yoon-Jae; Sung, Daeil; Oh, Eunhye; Jang, Seojin; Farrand, Lee; Van-Hai Hoang; Cong-Truong Nguyen; Ann, Jihyae; Lee, Jeewoo; Seo, Jae Hong
- Issue Date
- 2019
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- C-terminal HSP90 inhibitor; L80; Triple-negative breast cancer; Cancer stem cells; STAT3; Metastasis
- Citation
- CANCER LETTERS, v.447, pp.141 - 153
- Indexed
- SCIE
SCOPUS
- Journal Title
- CANCER LETTERS
- Volume
- 447
- Start Page
- 141
- End Page
- 153
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/68995
- DOI
- 10.1016/j.canlet.2019.01.029
- ISSN
- 0304-3835
- Abstract
- Triple-negative breast cancer (TNBC) is an aggressive heterogeneous disease with a divergent profile. It has an earlier tendency to form metastases and is associated with poor clinical outcomes due to the limited treatment options available. Heat-shock protein (HSP90) represents a potential treatment target as it promotes tumor progression and metastasis by modulating the maturation and stabilization of signal transduction proteins. We sought to investigate the efficacy of the C-terminal HSP90 inhibitor L80 on cell proliferation, breast cancer stem cell (BCSC)-like properties, tumor growth and metastasis. L80 suppressed cell viability and concomitantly inhibited AKT/MEK/ERK/JAK2/STAT3 signaling in TNBC cells but did not induce cytotoxicity in normal cells. L80 effectively targeted BCSC-like traits, together with significant reductions in the CD44high/CD24low-population, ALDH1 activity and mammosphere forming-ability. In support of the in vitro observations, L80 administration caused significant impairment in tumor growth, angiogenesis and distant metastases in an orthotopic allograft model with BCSC-enriched cells in vivo. These phenomena were associated with the suppression of BCSC-like characteristics and STAT3 dysfunction. Our findings highlight properties of the L80 compound that may be useful in suppressing metastatic TNBC.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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