SPON2 acts as a tumor promoter in HR-positive/HER2-negative breast cancer by regulating β-catenin signaling.

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical breast cancer Pub Date : 2025-08-07 DOI:10.1016/j.clbc.2025.07.030

Gu-Yue Liu, Dong-Ping Huang, Can Ge, Xiao-Yu Li, Fei Chen, Jia-Shu Fan, Huan-Ping Tu

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引用次数: 0

Abstract

Background: Spondin-2 (SPON2) expression is associated with various types of cancer, but its role in breast cancer (BC) remains ambiguous, especially in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) BC.

Methods: The expression of SPON2 in HR+/HER2- BC tissues and adjacent tissues was detected using immunohistochemical staining and western blotting. Cell proliferation and migration were assessed via CCK-8 assay, EdU assay, and transwell assay. Animal studies were performed to assess the effect of SPON2 knockdown on tumor growth.

Results: Herein, increased expression of SPON2 was found in HR+/HER2- BC, and silencing SPON2 suppressed cell proliferation, clonogenicity, and migration, whereas SPON2 overexpression had the opposite effects. Notably, SPON2 knockdown significantly suppressed tumor growth in a xenograft tumor assay. Mechanistically, a reduction in SPON2 expression inhibited β-catenin activation, whereas its overexpression promoted β-catenin-mediated proliferation and migration.

Conclusion: These data indicate that SPON2 plays oncogenic roles in HR+/HER2- BC via activating the β-catenin pathway, and may represent a potential therapeutic target for patients diagnosed with HR+/HER2- BC.

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SPON2通过调节β-catenin信号传导，在hr阳性/ her2阴性乳腺癌中作为肿瘤启动子。

背景：Spondin-2 （SPON2）的表达与多种类型的癌症有关，但其在乳腺癌（BC）中的作用尚不清楚，特别是在激素受体阳性(HR+)/人表皮生长因子受体2阴性（HER2-） BC中。方法：采用免疫组化染色和western blotting检测SPON2在HR+/HER2- BC组织及癌旁组织中的表达。通过CCK-8法、EdU法和transwell法检测细胞增殖和迁移。通过动物实验来评估SPON2敲低对肿瘤生长的影响。结果：在HR+/HER2- BC中发现SPON2表达增加，沉默SPON2可抑制细胞增殖、克隆性和迁移，而过表达SPON2则具有相反的作用。值得注意的是，在异种移植肿瘤实验中，SPON2敲低显著抑制肿瘤生长。从机制上讲，SPON2表达的减少抑制了β-catenin的激活，而其过表达促进了β-catenin介导的增殖和迁移。结论：这些数据表明，SPON2通过激活β-catenin通路在HR+/HER2- BC中发挥致癌作用，可能是HR+/HER2- BC患者的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical breast cancer 医学-肿瘤学

CiteScore

5.40

自引率

3.20%

发文量

174

审稿时长

48 days

期刊介绍： Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.