Primed atypical ductal hyperplasia-associated fibroblasts promote cell growth and polarity changes of transformed epithelium-like breast cancer MCF-7 cells via miR-200b/c-IKKβ signaling.

Primed atypical ductal hyperplasia-associated fibroblasts promote cell growth and polarity changes of transformed epithelium-like breast cancer MCF-7 cells via miR-200b/c-IKKβ signaling.
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DOI:
10.1038/s41419-017-0133-1
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发表时间:
2018-01-26
影响因子:
9
通讯作者:
Hou Y
Hou Y
中科院分区:
生物学1区
文献类型:
--
作者:
Sun Y;Yang D;Xi L;Chen Y;Fu L;Sun K;Yin J;Li X;Liu S;Qin Y;Liu M;Hou Y

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癌相关成纤维细胞(CAF)通过刺激癌细胞增殖和侵袭支持肿瘤发生,但癌前基质成纤维细胞如何触发上皮变化仍不清楚。我们证明非典型导管增生相关成纤维细胞(AHF)是一种活化的成纤维细胞,并作为CAFs样成纤维细胞刺激上皮样肿瘤细胞MCF-7的细胞生长和极性改变。微阵列显示miR-200 b和miR-200 c在AHF和CAF中下调,并有助于基质成纤维细胞活性。此外,miR-200 B/c与靶基因IKKβ(inhibitor of nuclear factor kappa-B kinase β,核因子-κ B激酶β抑制剂)一起调控派-1(plasminogen activator inhibitor-1,纤溶酶原激活物抑制剂-1)的表达,通过NF-κB途径调节MCF-7细胞的生长和极性改变。探讨AHF在癌前转化中的差异对于理解乳腺癌进展的病理生物学至关重要。
Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating cancer cell proliferation, and invasion, but how the premalignant stromal fibroblasts trigger epithelial changes remain unclear. We demonstrate that atypical ductal hyperplasia-associated fibroblasts (AHFs) are one kind of activated fibroblasts and stimulate cell growth and polarity change of epithelium-like tumor cell MCF-7 as CAFs-like fibroblasts. Microarray shows miR-200b and miR-200c are downregulated during AHFs and CAFs, and contribute to stromal fibroblast activity. Additionally, miR-200b/c with target gene IKKβ (inhibitor of nuclear factor kappa-B kinase β) control PAI-1 (plasminogen activator inhibitor-1) expression to regulate growth and polarity changes of MCF-7 cells through NF-κB pathway. Exploring the difference of AHFs in premalignant transformation is crucial for understanding the pathobiology of breast cancer progression.
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