Interleukin-31 Receptor α Is Required for Basal-Like Breast Cancer Progression.

Yanling He,Jian Shi,Weijun Pan,Fang Tai,Xinyuan Zhang,Li Liang

doi:10.3389/fonc.2020.00816

Abstract

Purpose: Interleukin-31 receptor α (IL31RA) usually mediates IL-31 induced inflammation and allergic diseases. However, the functional roles of IL-31/IL31RA signaling in basal-like breast cancer (BLBC) progression remain totally unclear.Methods: Tumorsphere formation, transwell, and wound healing assays were used to measure the BLBC progression. We implanted tumor cells in mammary fat pad and tail vein of nude mice to detect the growth and metastasis of BLBC cells. Luciferase and ChIP assays were employed to measure the transcriptional regulation. Western blot and real-time PCR assays as well as bio-informatics analyses were conducted to observe the expression of IL31RA.Results: We found that silencing of IL31RA suppresses the cancer stem cell-like properties, migration and invasion of BLBC cells in vitro as well as tumor growth and metastasis in vivo. Knockdown of IL31RA ameliorates IL-31-mediated pro-oncogenic functions. Overexpression of IL31RA in luminal breast cancer cells enhances the cancer stem cell-like properties and cell motility. Our data further identified IL31RA as a target gene of Twist/BRD4 transcription complex.Conclusion: Overall, these data indicate that IL31RA promotes basal-like breast cancer progression and metastasis, suggesting that targeting of IL-31/IL31RA axis might be beneficial to treatment of BLBC.

Highlights

Basal-like breast cancer (BLBC) is a cluster of breast tumor cells that characterized with low expression of estrogen receptor, progesterone receptor, and epidermal growth factor receptor 2; it frequently occurs in young women and has higher incidence rates of distant organ metastasis and recurrence than hormone receptor positive breast cancer
We found that IL31RA is required for cancer stem cell (CSC)-like properties, invasion and metastasis of BLBC cells, implicating that specific targeting of this protein represents a potential therapy for BLBC treatment
To reveal the pathological role of IL31RA in BLBC, we knocked down IL31RA gene in MDA-MB-231 and MDAMB-157 BLBC cell lines and constructed their stable clones

Summary

Introduction

Basal-like breast cancer (BLBC) is a cluster of breast tumor cells that characterized with low expression of estrogen receptor, progesterone receptor, and epidermal growth factor receptor 2; it frequently occurs in young women and has higher incidence rates of distant organ metastasis and recurrence than hormone receptor positive breast cancer. BLBC is insensitive to endocrine or HER2-targeted therapies with low 5-year survival rates. BLBC is an inflammation-associated disease, its rapid growth and metastasis heavily relies on aberrant up-regulation of pro-oncogenic inflammatory pathways [4]. Plenty of studies have observed that two critical cytokines, IL-6 and IL-8, are up-regulated in BLBC which are required for maintenance of breast cancer stem cell-like properties [5]. BLBC has high level of infiltration of tumor associated macrophage and lymphocytes compared

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Conclusion