期刊
CANCER BIOLOGY & THERAPY
卷 20, 期 3, 页码 328-337出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2018.1529101
关键词
FSTL1; chemoresistance; stemness; breast cancer; integrin beta 3; Wnt signaling; miR-137
类别
资金
- Natural Science Foundation of Heilongjiang Province [ZD2016018]
- National Natural Science Foundation of China [81673006]
FSTL1 is a protein coding gene associated with cell signaling pathway regulation and the progression of a variety of disorders. In this study, we hypothesized that FSTL1 increases oncogenesis in breast cancer by enhancing stemness and chemoresistance. RT-PCR and IHC revealed significantly higher FSTL1 mRNA and protein levels in TNBC than in non-TNBC specimens and in breast cancer cell lines. We then found that FSTL1 levels were significantly increased in chemoresistant cells. LIVE/DEAD, MTT cell viability and colony formation assays did in fact demonstrate that FSTL1 is required for CDDP and DOX chemoresistance in breast cancer cell lines. FSTL1 overexpression caused significant elevation of stem cell biomarkers, as well as breast cancer cell proliferation. To determine whether the Wnt/beta-catenin signaling pathway is involved in the observed effects of FSTL1, we assessed levels of pathway target. TOP/FOP flash, colony formation, and tumor sphere formation assays indicated that FSTL1 activates Wnt/beta-catenin signaling through integrin beta 3. We then sought to identify a microRNA (miRNA) that regulates FSTL1 activity. Luciferase assays demonstrated that miR-137 reduces FSTL1 mRNA and protein levels. Ultimately, our findings indicate that there is an miR-137/FSTL1/integrin beta 3/Wnt/beta-catenin signaling axis in breast cancer cells that regulates stemness and chemoresistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据