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A Luminacin D Analog HL142 Inhibits Ovarian Tumor Growth and Metastasis by Reversing EMT and Attenuating the TGFβ and FAK Pathways
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| Title: | A Luminacin D Analog HL142 Inhibits Ovarian Tumor Growth and Metastasis by Reversing EMT and Attenuating the TGFβ and FAK Pathways |
| Authors: | Wang, Baojin Browse this author | | Li, Hanxuan Browse this author | | Zhao, Xinxin Browse this author | | Zhang, Wenjing Browse this author | | Zhao, Guannan Browse this author | | Wu, Zhongzhi Browse this author | | Zhang, Ruitao Browse this author | | Dong, Peixin Browse this author →KAKEN DB | | Watari, Hidemichi Browse this author | | Tigyi, Gabor Browse this author | | Li, Wei Browse this author | | Yue, Junming Browse this author |
| Keywords: | Luminacin D analog | | HL142 | | EMT | | ovarian tumor | | metastasis | | ASAP1 | | FAK |
| Issue Date: | 25-Jul-2021 |
| Journal Title: | Journal of Cancer |
| Volume: | 12 |
| Issue: | 18 |
| Start Page: | 5654 |
| End Page: | 5663 |
| Publisher DOI: | 10.7150/jca.61066 |
| Abstract: | 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. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82492 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 董 培新
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