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
{"title":"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。","authors":"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","doi":"10.1111/jcmm.70870","DOIUrl":null,"url":null,"abstract":"<p>Understanding the role and molecular regulation of genes associated with tumour cell motility may be informative for future cancer therapy development. <i>Sperm-associated antigen 6</i> (<i>SPAG6</i>) 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 <i>SPAG6</i> promoter hypermethylation in all molecular subtypes. Immunohistochemistry on the independent WSG PlanB breast cancer cohort (<i>n</i> = 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 (<i>p</i> < 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.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT01049425</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 19","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70870","citationCount":"0","resultStr":"{\"title\":\"The Janus Face of SPAG6: Inducing EMT in Luminal Breast Cancer Cells Amidst Widespread Expression Loss in Breast Tumours\",\"authors\":\"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\",\"doi\":\"10.1111/jcmm.70870\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Understanding the role and molecular regulation of genes associated with tumour cell motility may be informative for future cancer therapy development. <i>Sperm-associated antigen 6</i> (<i>SPAG6</i>) 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 <i>SPAG6</i> promoter hypermethylation in all molecular subtypes. Immunohistochemistry on the independent WSG PlanB breast cancer cohort (<i>n</i> = 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 (<i>p</i> < 0.0001) and characteristics of epithelial-mesenchymal transition (EMT) with actin and E-cadherin displacement. 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The Janus Face of SPAG6: Inducing EMT in Luminal Breast Cancer Cells Amidst Widespread Expression Loss in Breast Tumours
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.
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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.
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