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. Trial Registration: ClinicalTrials.gov identifier: NCT01049425.

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• Villwock, S.
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• Berger, J.
• Schalla, C.
• von Serenyi, S.
• Dietrich, J.
• Ortiz-Brüchle, N.
• Heij, L.
• Bednarsch, J.
• Gluz, O.
• Nitz, U.
• Harbeck, N.
• Graeser, M.
• Zu Eulenburg, C.
• Mohammadian, M. P.
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• Kreipe, H. H.
• Christgen, M.
• Radner, M.
• Jonigk, D.
• Dahl, E.