A Luminacin D Analog HL142 Inhibits Ovarian Tumor Growth and Metastasis by Reversing EMT and Attenuating the TGFβ and FAK Pathways

Wang, Baojin; Li, Hanxuan; Zhao, Xinxin et al.

Journal of Cancer, 2021, 12(18), 5654-5663

Permalink : https://hdl.handle.net/2115/82492

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アクセス権
open access
URI
https://hdl.handle.net/2115/82492
タイトル
A Luminacin D Analog HL142 Inhibits Ovarian Tumor Growth and Metastasis by Reversing EMT and Attenuating the TGFβ and FAK Pathways
著者
Wang, Baojin ; Li, Hanxuan ; Zhao, Xinxin ; Zhang, Wenjing ; Zhao, Guannan ; Wu, Zhongzhi ; Zhang, Ruitao ; Dong, Peixin ; Watari, Hidemichi ; Tigyi, Gabor ; Li, Wei ; Yue, Junming
著者名
Wang, Baojin
著者名
Li, Hanxuan
著者名
Zhao, Xinxin
著者名
Zhang, Wenjing
著者名
Zhao, Guannan
著者名
Wu, Zhongzhi
著者名
Zhang, Ruitao
e-Rad_Researcher
50602504
著者名
Dong, Peixin
著者名
Watari, Hidemichi
著者名
Tigyi, Gabor
著者名
Li, Wei
著者名
Yue, Junming
言語
英語
キーワード
Luminacin D analog
HL142
EMT
ovarian tumor
metastasis
ASAP1
FAK
発行日
2021-07-25
収録物名
Journal of Cancer
巻(号)
12(18)
ページ
5654-5663
抄録
Epithelial to mesenchymal transition (EMT) is known to contribute to tumor metastasis and chemoresistance. Reversing EMT using small molecule inhibitors to target EMT associated gene expression represents an effective strategy for cancer treatment. The purpose of this study is to test whether a new luminacin D analog HL142 reverses EMT in ovarian cancer (OC) and has the therapeutic potential for OC. We chemically synthesized HL142 and tested its functions in OC cells in vitro and its efficacy in inhibiting ovarian tumor growth and metastasis in vivo using orthotopic OC mouse models.We first demonstrate that ASAP1 is co-amplified and interacts with the focal adhesion kinase (FAK) protein in serous ovarian carcinoma. HL142 inhibits ASAP1 and its interaction protein FAK in highly invasive OVCAR8 and moderately invasive OVCAR3 cells. HL142 inhibits EMT phenotypic switch, accompanied by upregulating epithelial marker E-cadherin and cytokeratin-7 and downregulating mesenchymal markers vimentin, β-catenin, and snail2 in both cell lines. Functionally, HL142 inhibits proliferation, colony formation, migration, and invasion. HL142 also sensitizes cell responses to chemotherapy drug paclitaxel treatment and inhibits ovarian tumor growth and metastasis in orthotopic OC mouse models. We further show that HL142 attenuates the TGFβ and FAK pathways in vitro using OC cells and in vivousing orthotopic mouse models.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution 4.0 International
PISSN
1837-9664
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.7150/jca.61066