MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells
Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor ce...
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MDPI AG
2020-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/1/9 |
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| author | Dansaem Lim Jin Gu Cho Eunsik Yun Aram Lee Hong-Yeoul Ryu Young Joo Lee Sukjoon Yoon Woochul Chang Myeong-Sok Lee Byung Su Kwon Jongmin Kim |
| author_facet | Dansaem Lim Jin Gu Cho Eunsik Yun Aram Lee Hong-Yeoul Ryu Young Joo Lee Sukjoon Yoon Woochul Chang Myeong-Sok Lee Byung Su Kwon Jongmin Kim |
| author_sort | Dansaem Lim |
| collection | DOAJ |
| description | Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial–mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a–AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization. |
| first_indexed | 2024-03-10T13:49:16Z |
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| id | doaj.art-45aae6f1de8b45de8a8466ff45fe5973 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T13:49:16Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-45aae6f1de8b45de8a8466ff45fe59732023-11-21T02:18:08ZengMDPI AGGenes2073-44252020-12-01121910.3390/genes12010009MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer CellsDansaem Lim0Jin Gu Cho1Eunsik Yun2Aram Lee3Hong-Yeoul Ryu4Young Joo Lee5Sukjoon Yoon6Woochul Chang7Myeong-Sok Lee8Byung Su Kwon9Jongmin Kim10Division of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaDivision of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaDivision of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaDivision of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaSchool of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, College of National Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Obstetrics and Gynecology, Kyung Hee University Medical Center, 23, Seoul 02447, KoreaDivision of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaDepartment of Biology Education, College of Education, Pusan National University, Busan 46241, KoreaDivision of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaDepartment of Obstetrics and Gynecology, Kyung Hee University Medical Center, 23, Seoul 02447, KoreaDivision of Biological Sciences, Sookmyung Women’s University, Seoul 04310, KoreaTargeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial–mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a–AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.https://www.mdpi.com/2073-4425/12/1/9breast cancervasculogenic mimicryepithelial–mesenchymal transitionAXLmiR-34a |
| spellingShingle | Dansaem Lim Jin Gu Cho Eunsik Yun Aram Lee Hong-Yeoul Ryu Young Joo Lee Sukjoon Yoon Woochul Chang Myeong-Sok Lee Byung Su Kwon Jongmin Kim MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells Genes breast cancer vasculogenic mimicry epithelial–mesenchymal transition AXL miR-34a |
| title | MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells |
| title_full | MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells |
| title_fullStr | MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells |
| title_full_unstemmed | MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells |
| title_short | MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells |
| title_sort | microrna 34a axl axis regulates vasculogenic mimicry formation in breast cancer cells |
| topic | breast cancer vasculogenic mimicry epithelial–mesenchymal transition AXL miR-34a |
| url | https://www.mdpi.com/2073-4425/12/1/9 |
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