当前位置: X-MOL 学术Cell Commun. Signal. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1.
Cell Communication and Signaling ( IF 8.2 ) Pub Date : 2020-09-07 , DOI: 10.1186/s12964-020-00646-2
Ping Yin 1 , Yu Bai 1, 2 , Zhuo Wang 1 , Yu Sun 1 , Jian Gao 1 , Lei Na 1 , Zhongbo Zhang 1 , Wei Wang 1 , Chenghai Zhao 1
Affiliation  

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.

中文翻译:

非规范 Fzd7 信号传导有助于涉及 Col6a1 的乳腺癌间充质样干细胞。

间充质样干细胞的特征是上皮间质转化 (EMT)。乳腺癌 (BC) 细胞间充质样干细胞负责远端肺转移。对数据库的询问表明 Fzd7 与一组间充质相关基因和一组干性相关基因密切相关。间充质样 MDA-MB-231 和 Hs578T 细胞中的 Fzd7 敲低降低了波形蛋白、Slug 和 Zeb1 的表达,诱导了上皮样形态,抑制了细胞运动,损害了乳腺球形成并减少了 Lgr5+ 亚群。相比之下,MCF7 细胞中的 Fzd7 过表达导致相反的变化。Fzd7 敲低延迟了异种移植肿瘤的形成,抑制了肿瘤生长,并损害了肺转移。从机制上讲,Fzd7 与 Wnt5a/b 结合并调节磷酸化 Stat3(p-STAT3)的表达,Smad3 和 Yes 相关蛋白 1 (Yap1)。此外,Fzd7-Wnt5b 调节胶原蛋白 VI 型 alpha 1 (Col6a1) 的表达。Wnt5b 敲低和 Col6a1 敲低都破坏了 BC 细胞间充质表型和干细胞。总之,Fzd7 有助于 BC 细胞 EMT 和干性,主要通过非经典 Wnt5b 途径诱导肿瘤发生和转移。Col6a1 与 Fzd7-Wnt5b 信号传导有关,并介导 Fzd7-Wnt5b 诱导的间充质样干细胞。
更新日期:2020-09-08
down
wechat
bug