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Published on: January 18, 2017
TFPI inhibits breast cancer progression by suppressing ERK/p38 MAPK signaling pathway
Mengying Xing1, Ying Yang1, Jiaxue Huang1
1Department of Medical Genetics, School of Basic Medical Sciences, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, People's Republic of China.
Background:
Tissue factor pathway inhibitor-1 (TFPI) is a serine protease inhibitor, which is responsible for inactivating TF-induced coagulation. Recently, increasing studies revealed that TFPI was lowly expressed in tumor cells and exhibited the antitumor activity.
Objective:
The aim of this study was to explore the role and underlying molecular mechanisms of TFPI in breast cancer.
Methods:
The expression and prognostic value of TFPI were analyzed using UALCAN and Kaplan-Meier plotter website. The expression level of TFPI in breast cancer tissues and cells was examined by immunohistochemistry (IHC) and western blot analysis, respectively. Cellular proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were determined by transwell assay. The methylation level of TFPI promoter was determined by methylation-specific PCR.
Results:
TFPI expression was significantly lower in breast cancer tissues and cells compared to normal breast tissues and normal breast cells. Patients with low TFPI levels showed worse overall survival (OS). Furthermore, overexpression of TFPI significantly inhibited the proliferation, migration and invasion of breast cancer cells. Conversely, knockdown of TFPI promoted the proliferation, migration and invasion of breast cancer cells. Mechanistically, TFPI inhibited the ERK/p38 MAPK signaling pathway in breast cancer. Moreover, DNA hypermethylation of TFPI promoter was responsible for the downregulation of TFPI in breast cancer cells.
Conclusion:
TFPI inhibited breast cancer cell proliferation, migration and invasion through inhibition of the ERK/p38 MAPK signaling pathway, suggesting that TFPI may serve as a novel prognostic biomarker and therapeutic target for breast cancer.
Insights
Tissue factor pathway inhibitor-1 (TFPI) is downregulated in breast cancer, correlating with worse survival. TFPI inhibits cancer cell proliferation, migration, and invasion by affecting the ERK/p38 MAPK pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tissue factor pathway inhibitor-1 (TFPI) is a key regulator of coagulation.
- Emerging evidence suggests TFPI possesses antitumor properties.
- TFPI expression is often reduced in various cancer types.
Purpose of the Study:
- To investigate the role of TFPI in breast cancer.
- To elucidate the molecular mechanisms underlying TFPI's function in breast cancer.
- To assess TFPI as a potential prognostic biomarker and therapeutic target.
Main Methods:
- Bioinformatic analysis using UALCAN and Kaplan-Meier plotter.
- Immunohistochemistry and Western blot for TFPI expression.
- Cell proliferation, migration, and invasion assays (CCK-8, colony formation, transwell).
- Methylation-specific PCR to assess promoter methylation.
Main Results:
- TFPI expression is significantly decreased in breast cancer tissues and cells.
- Low TFPI levels correlate with poorer overall survival.
- TFPI overexpression inhibits, while knockdown promotes, breast cancer cell proliferation, migration, and invasion.
- TFPI acts by inhibiting the ERK/p38 MAPK signaling pathway.
- DNA hypermethylation of the TFPI promoter contributes to its downregulation.
Conclusions:
- TFPI suppresses breast cancer progression by inhibiting the ERK/p38 MAPK pathway.
- TFPI demonstrates potential as a prognostic biomarker for breast cancer.
- TFPI represents a promising therapeutic target for breast cancer treatment.
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