FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway
Abstract Background Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-021-01866-3 |
| _version_ | 1818419492630298624 |
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| author | Dilihumaer Tuluhong Tao Chen Jingjie Wang Huijuan Zeng Hanjun Li Wangmu Dunzhu Qiurong Li Shaohua Wang |
| author_facet | Dilihumaer Tuluhong Tao Chen Jingjie Wang Huijuan Zeng Hanjun Li Wangmu Dunzhu Qiurong Li Shaohua Wang |
| author_sort | Dilihumaer Tuluhong |
| collection | DOAJ |
| description | Abstract Background Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor 2 (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our current study was to detect the functions of FZD2 in BC and explore its underlying molecular mechanism. Methods The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC), respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were separately conducted to detect cell viability, invasion, migration, apoptosis and cell cycle distribution. The levels of Epithelial-mesenchymal transition (EMT) biomarkers were examined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo. Results FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis in BC patients. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT process in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway. Conclusion FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway. |
| first_indexed | 2024-12-14T12:39:26Z |
| format | Article |
| id | doaj.art-f7d04162973e4229ab745ea3a94ec9fc |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-14T12:39:26Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-f7d04162973e4229ab745ea3a94ec9fc2022-12-21T23:00:57ZengBMCCancer Cell International1475-28672021-04-0121111310.1186/s12935-021-01866-3FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathwayDilihumaer Tuluhong0Tao Chen1Jingjie Wang2Huijuan Zeng3Hanjun Li4Wangmu Dunzhu5Qiurong Li6Shaohua Wang7Department of General Surgery, Jinling Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Jinling Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Jinling Hospital, Medical School of Nanjing UniversityDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of General Surgery, Jinling Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Jinling Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Jinling Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Jinling Hospital, Medical School of Nanjing UniversityAbstract Background Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor 2 (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our current study was to detect the functions of FZD2 in BC and explore its underlying molecular mechanism. Methods The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC), respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were separately conducted to detect cell viability, invasion, migration, apoptosis and cell cycle distribution. The levels of Epithelial-mesenchymal transition (EMT) biomarkers were examined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo. Results FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis in BC patients. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT process in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway. Conclusion FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.https://doi.org/10.1186/s12935-021-01866-3Breast cancerFZD2Poor prognosisEMTNotch signaling pathway |
| spellingShingle | Dilihumaer Tuluhong Tao Chen Jingjie Wang Huijuan Zeng Hanjun Li Wangmu Dunzhu Qiurong Li Shaohua Wang FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway Cancer Cell International Breast cancer FZD2 Poor prognosis EMT Notch signaling pathway |
| title | FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway |
| title_full | FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway |
| title_fullStr | FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway |
| title_full_unstemmed | FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway |
| title_short | FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway |
| title_sort | fzd2 promotes tgf β induced epithelial to mesenchymal transition in breast cancer via activating notch signaling pathway |
| topic | Breast cancer FZD2 Poor prognosis EMT Notch signaling pathway |
| url | https://doi.org/10.1186/s12935-021-01866-3 |
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