Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1
Abstract Mesenchymal-like stemness is characterized by epithelial-mesenchymal transition (EMT). Breast cancer (BC) cell mesenchymal-like stemness is responsible for distal lung metastasis. Interrogation of databases showed that Fzd7 was closely associated with a panel of mesenchymal-related genes an...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12964-020-00646-2 |
| _version_ | 1818302309406343168 |
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| author | Ping Yin Yu Bai Zhuo Wang Yu Sun Jian Gao Lei Na Zhongbo Zhang Wei Wang Chenghai Zhao |
| author_facet | Ping Yin Yu Bai Zhuo Wang Yu Sun Jian Gao Lei Na Zhongbo Zhang Wei Wang Chenghai Zhao |
| author_sort | Ping Yin |
| collection | DOAJ |
| description | Abstract Mesenchymal-like stemness is characterized by epithelial-mesenchymal transition (EMT). Breast cancer (BC) cell mesenchymal-like stemness is responsible for distal lung metastasis. Interrogation of databases showed that Fzd7 was closely associated with a panel of mesenchymal-related genes and a panel of stemness-related genes. Fzd7 knockdown in mesenchymal-like MDA-MB-231 and Hs578T cells reduced expression of Vimentin, Slug and Zeb1, induced an epithelial-like morphology, inhibited cell motility, impaired mammosphere formation and decreased Lgr5+ subpopulation. In contrast, Fzd7 overexpression in MCF7 cells resulted in opposite changes. Fzd7 knockdown delayed xenograft tumor formation, suppressed tumor growth, and impaired lung metastasis. Mechanistically, Fzd7 combined with Wnt5a/b and modulated expression of phosphorylated Stat3 (p-STAT3), Smad3 and Yes-associated protein 1 (Yap1). Moreover, Fzd7-Wnt5b modulated expression of collagen, type VI, alpha 1 (Col6a1). Both Wnt5b knockdown and Col6a1 knockdown disrupted BC cell mesenchymal phenotype and stemness. Taken together, Fzd7 contributes to BC cell EMT and stemness, inducing tumorigenesis and metastasis, mainly through a non-canonical Wnt5b pathway. Col6a1 is implicated in Fzd7-Wnt5b signaling, and mediates Fzd7-Wnt5b -induced mesenchymal-like stemness. Video Abstract |
| first_indexed | 2024-12-13T05:36:51Z |
| format | Article |
| id | doaj.art-2c9b534540694bd6af650d8bb3565fb7 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-13T05:36:51Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-2c9b534540694bd6af650d8bb3565fb72022-12-21T23:57:54ZengBMCCell Communication and Signaling1478-811X2020-09-0118111310.1186/s12964-020-00646-2Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1Ping Yin0Yu Bai1Zhuo Wang2Yu Sun3Jian Gao4Lei Na5Zhongbo Zhang6Wei Wang7Chenghai Zhao8Department of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityDepartment of Pathophysiology, College of Basic Medical Science, China Medical UniversityAbstract Mesenchymal-like stemness is characterized by epithelial-mesenchymal transition (EMT). Breast cancer (BC) cell mesenchymal-like stemness is responsible for distal lung metastasis. Interrogation of databases showed that Fzd7 was closely associated with a panel of mesenchymal-related genes and a panel of stemness-related genes. Fzd7 knockdown in mesenchymal-like MDA-MB-231 and Hs578T cells reduced expression of Vimentin, Slug and Zeb1, induced an epithelial-like morphology, inhibited cell motility, impaired mammosphere formation and decreased Lgr5+ subpopulation. In contrast, Fzd7 overexpression in MCF7 cells resulted in opposite changes. Fzd7 knockdown delayed xenograft tumor formation, suppressed tumor growth, and impaired lung metastasis. Mechanistically, Fzd7 combined with Wnt5a/b and modulated expression of phosphorylated Stat3 (p-STAT3), Smad3 and Yes-associated protein 1 (Yap1). Moreover, Fzd7-Wnt5b modulated expression of collagen, type VI, alpha 1 (Col6a1). Both Wnt5b knockdown and Col6a1 knockdown disrupted BC cell mesenchymal phenotype and stemness. Taken together, Fzd7 contributes to BC cell EMT and stemness, inducing tumorigenesis and metastasis, mainly through a non-canonical Wnt5b pathway. Col6a1 is implicated in Fzd7-Wnt5b signaling, and mediates Fzd7-Wnt5b -induced mesenchymal-like stemness. Video Abstracthttp://link.springer.com/article/10.1186/s12964-020-00646-2Frizzled 7StemnessBreast cancerLgr5Wnt |
| spellingShingle | Ping Yin Yu Bai Zhuo Wang Yu Sun Jian Gao Lei Na Zhongbo Zhang Wei Wang Chenghai Zhao Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1 Cell Communication and Signaling Frizzled 7 Stemness Breast cancer Lgr5 Wnt |
| title | Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1 |
| title_full | Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1 |
| title_fullStr | Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1 |
| title_full_unstemmed | Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1 |
| title_short | Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1 |
| title_sort | non canonical fzd7 signaling contributes to breast cancer mesenchymal like stemness involving col6a1 |
| topic | Frizzled 7 Stemness Breast cancer Lgr5 Wnt |
| url | http://link.springer.com/article/10.1186/s12964-020-00646-2 |
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