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Updated: Jan 15, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
The Janus Face of SPAG6: Inducing EMT in Luminal Breast Cancer Cells Amidst Widespread Expression Loss in Breast
Antonio Sechi1, Jolein Mijnes2,3, Sophia Villwock2,3
1Department of Cell and Tumor Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
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.
Insights
Sperm-associated antigen 6 (SPAG6) gene hypermethylation is linked to breast cancer progression. SPAG6 down-regulation promotes tumor cell migration and epithelial-mesenchymal transition (EMT), suggesting a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor cell motility is crucial for cancer progression and metastasis.
- Understanding the molecular regulation of motility-associated genes can inform cancer therapy.
- Sperm-associated antigen 6 (SPAG6) is a conserved motility protein implicated in cancer.
Purpose of the Study:
- To investigate the role and molecular regulation of SPAG6 in breast cancer.
- To determine the impact of SPAG6 on tumor cell migration and epithelial-mesenchymal transition (EMT).
Main Methods:
- In silico analysis of The Cancer Genome Atlas (TCGA) data for SPAG6 promoter methylation.
- Immunohistochemistry on a large independent breast cancer cohort (n=2241).
- In vitro studies using luminal breast cancer cells to assess SPAG6 overexpression effects.
Main Results:
- Tumor-specific SPAG6 promoter hypermethylation was observed across all breast cancer molecular subtypes.
- SPAG6 protein levels were comprehensively down-regulated in breast tumors.
- SPAG6 overexpression in luminal cells significantly increased migration capacity and induced EMT characteristics.
Conclusions:
- SPAG6 plays a significant role in promoting tumor cell migration and EMT in luminal breast cancer.
- SPAG6 down-regulation via promoter hypermethylation contributes to breast cancer progression.
- SPAG6 represents a potential therapeutic target for inhibiting breast cancer metastasis.
