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

Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep Subsets: MEDLINE

Original Publication: Athens, Greece : D. A. Spandidos

Membrane Proteins/*metabolism ; Triple Negative Breast Neoplasms/*metabolism ; Wnt Signaling Pathway/*physiology; Cancer-Associated Fibroblasts/metabolism ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; China ; Databases, Genetic ; Gene Expression/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/physiology ; Neoplasm Invasiveness/genetics ; Prognosis ; Transcriptome/genetics ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/physiopathology ; Wnt Signaling Pathway/genetics ; beta Catenin/genetics ; beta Catenin/metabolism

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.

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Keywords: Wnt/β‑catenin signalling pathway; cancer‑associated fibroblasts; leucine‑rich repeat‑containing protein 15; triple‑negative basal‑like breast cancer

0 (CTNNB1 protein, human)
0 (LRRC15 protein, human)
0 (Membrane Proteins)
0 (beta Catenin)

Date Created: 20211102 Date Completed: 20220221 Latest Revision: 20220221

20221213

PMC8600416

10.3892/mmr.2021.12518

34726255