The Janus Face of SPAG6: Inducing EMT in Luminal Breast Cancer Cells Amidst Widespread Expression Loss in Breast Tumours

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-10-09 DOI:10.1111/jcmm.70870

Antonio Sechi, Jolein Mijnes, Sophia Villwock, Michael Rose, Florian Steib, Sarah Bringezu, Jonas Berger, Carmen Schalla, Sonja von Serenyi, Jana Dietrich, Nadina Ortiz-Brüchle, Lara Heij, Jan Bednarsch, Oleg Gluz, Ulrike Nitz, Nadia Harbeck, Monika Graeser, Christine zu Eulenburg, Mohammad Parsa Mohammadian, Katarzyna Jóźwiak, Hans-Heinrich Kreipe, Matthias Christgen, Martin Radner, Danny Jonigk, Edgar Dahl

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Abstract

Understanding the role and molecular regulation of genes associated with tumour cell motility may be informative for future cancer therapy development. Sperm-associated antigen 6 (SPAG6) gene, encoding an evolutionarily highly conserved flagellar motility protein, is regulated by promoter hypermethylation in breast cancer. Our in silico analysis of healthy and breast cancer tissues from The Cancer Genome Atlas (TCGA) showed tumour-specific SPAG6 promoter hypermethylation in all molecular subtypes. Immunohistochemistry on the independent WSG PlanB breast cancer cohort (n = 2241) confirmed comprehensive down-regulation of SPAG6 on the protein level. In vitro models demonstrated that SPAG6 overexpression in luminal cells exhibited strongly increased migration capacity (p < 0.0001) and characteristics of epithelial-mesenchymal transition (EMT) with actin and E-cadherin displacement. We propose that SPAG6 may have an important role in triggering the EMT program in luminal breast cancer cells, driving tumour progression and metastasis.

Trial Registration: ClinicalTrials.gov identifier: NCT01049425

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SPAG6的双面面：在乳腺肿瘤中广泛表达缺失的情况下在腔内乳腺癌细胞中诱导EMT。

了解与肿瘤细胞运动相关的基因的作用和分子调控可能为未来的癌症治疗发展提供信息。精子相关抗原6 （SPAG6）基因编码一种在进化上高度保守的鞭毛运动蛋白，在乳腺癌中受启动子超甲基化调控。我们对来自癌症基因组图谱（TCGA）的健康和乳腺癌组织的计算机分析显示，肿瘤特异性SPAG6启动子在所有分子亚型中都存在高甲基化。独立WSG PlanB乳腺癌队列（n = 2241）的免疫组化证实SPAG6在蛋白水平上的全面下调。体外模型表明，在腔细胞中过表达SPAG6表现出强烈的迁移能力(p

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来源期刊

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

CiteScore

11.50

自引率

0.00%

发文量

期刊介绍： The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.