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Updated: Mar 5, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in
Hansol Bae1, Byungtak Kim1, Hyunkyung Lee1
1Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
Abstract:
To identify dysregulated genes by abnormal methylation and expression in breast cancer, we genome-wide analyzed methylation and expression microarray data from the Gene Expression Omnibus and the Cancer Genome Atlas database. One of the genes screened in silico, FLRT2, showed hypermethylation and downregulation in the cancer dataset and the association was verified both in cultured cell lines and cancer patients' tissue. To investigate the role of FLRT2 in breast cancer, its expression was knocked down and upregulated in mammary cell lines, and the effect was examined through three levels of approach: pathway analysis; cell activities such as proliferation, colony formation, migration, and adhesion; target gene expression. The top pathway was "Cellular growth and proliferation", or "Cancer"-related function, with the majority of the genes deregulated in a direction pointing to FLRT2 as a potential tumor suppressor. Concordantly, downregulation of FLRT2 increased cell proliferation and cell migration, while overexpression of FLRT2 had the opposite effect. Notably, cell adhesion was significantly decreased by FLRT2 in the collagen I-coated plate. Taken together, our results provide insights into the role of FLRT2 as a novel tumor suppressor in the breast, which is inactivated by hypermethylation during tumor development.
Insights
FLRT2 is a gene that acts as a tumor suppressor in breast cancer. It becomes hypermethylated and downregulated, promoting cancer growth and migration.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant gene methylation and expression are hallmarks of cancer development.
- Identifying novel genes involved in breast cancer pathogenesis is crucial for therapeutic strategies.
Purpose of the Study:
- To identify genes dysregulated by abnormal methylation and expression in breast cancer.
- To investigate the functional role of FLRT2 as a potential tumor suppressor in breast cancer.
Main Methods:
- Genome-wide analysis of methylation and expression microarray data from public databases (GEO, TCGA).
- In silico screening, in vitro studies using cell lines (knockdown/upregulation), and analysis of patient tissues.
- Pathway analysis, assessment of cell proliferation, colony formation, migration, adhesion, and target gene expression.
Main Results:
- FLRT2 exhibited hypermethylation and downregulation in breast cancer datasets and patient tissues.
- Downregulation of FLRT2 enhanced cell proliferation and migration, while its overexpression suppressed these processes.
- FLRT2 significantly decreased cell adhesion on collagen I and was linked to "Cellular growth and proliferation" pathways.
Conclusions:
- FLRT2 functions as a novel tumor suppressor in breast cancer.
- Hypermethylation-induced inactivation of FLRT2 contributes to breast tumor development.
- FLRT2 represents a potential therapeutic target for breast cancer treatment.
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