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癌相关成纤维细胞衍生的 LRRC15 通过调节 Wnt/β-连环蛋白信号通路促进三阴性乳腺癌细胞的迁移和侵袭。

Cancer‑associated fibroblast‑derived LRRC15 promotes the migration and invasion of triple‑negative breast cancer cells via Wnt/β‑catenin signalling pathway regulation.

机构信息

Department of Breast and Thyroid Surgery, Dongying People's Hospital, Dongying, Shandong 257091, P.R. China.

出版信息

Mol Med Rep. 2022 Jan;25(1). doi: 10.3892/mmr.2021.12518. Epub 2021 Nov 2.

Abstract

Triple‑negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The function of leucine‑rich repeat‑containing protein 15 (LRRC15), a member of the leucine‑rich repeat superfamily, in TNBC has not yet been elucidated. The aim of this study was to identify the combined role of LRRC15 and Wnt/β‑catenin signalling pathway in the development of TNBC. The expression of LRRC15 in TNBC tissues was analysed using data from The Cancer Genome Atlas. Cell migration and invasion assays were conducted to study the function of LRRC15 in TNBC. The expression of Wnt/β‑catenin signalling proteins was analysed via western blotting. The effect of LRRC15 on β‑catenin nuclear localisation was measured by performing western blotting and luciferase assays. It was found that high LRRC15 expression was associated with poor prognosis in patients with TNBC. High expression of LRRC15 in cancer‑associated fibroblasts (CAFs) promoted cell migration and invasion in TNBC cells. In addition, TNBC cells with LRRC15 overexpression in CAFs showed an aberrant increase in β‑catenin activity concomitant with nuclear localisation of β‑catenin, which inhibited its degradation. These results showed that LRRC15 promoted tumour migration and invasion in TNBC cells by regulating the Wnt/β‑catenin signalling pathway.

摘要

三阴性乳腺癌(TNBC)是一种侵袭性高、预后差的肿瘤亚型。富含亮氨酸重复蛋白 15(LRRC15)是亮氨酸重复超家族的成员,其在 TNBC 中的功能尚未阐明。本研究旨在探讨 LRRC15 与 Wnt/β-catenin 信号通路在 TNBC 发生发展中的共同作用。利用癌症基因组图谱的数据分析了 LRRC15 在 TNBC 组织中的表达情况。通过细胞迁移和侵袭实验研究了 LRRC15 在 TNBC 中的功能。通过 Western blot 分析了 Wnt/β-catenin 信号蛋白的表达。通过 Western blot 和荧光素酶实验测定了 LRRC15 对β-catenin 核定位的影响。结果发现,LRRC15 高表达与 TNBC 患者预后不良有关。CAFs 中 LRRC15 的高表达促进了 TNBC 细胞的迁移和侵袭。此外,CAFs 中过表达 LRRC15 的 TNBC 细胞表现出β-catenin 活性的异常增加,同时伴有β-catenin 的核定位,从而抑制其降解。这些结果表明,LRRC15 通过调节 Wnt/β-catenin 信号通路促进了 TNBC 细胞的迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8600416/ec07378cae3d/mmr-25-01-12518-g00.jpg

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