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Updated: Dec 25, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TFPI2 suppresses breast cancer progression through inhibiting TWIST-integrin α5 pathway
Danyi Zhao1, Jingjing Qiao1, Hongmei He1
1Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, No.467 Zhongshan Road, Shahekou District, Dalian City, 116027, Liaoning Province, China.
Background:
Tissue factor pathway inhibitor 2 (TFPI2) participates in carcinogenesis of various tumors, and is associated with poor survival of breast cancer patients. However, the effect and underlying mechanism of TFPI2 on breast cancer progression remains to be investigated.
Methods:
The expression level of TFPI2 in breast cancer tissues and cell lines was examined via qRT-PCR (quantitative real-time polymerase chain reaction) and immunohistochemistry. CCK8 (Cell Counting Kit-8), colony formation, wound healing or transwell assays were used to detect cell viability, proliferation, migration or invasion, respectively. In vivo subcutaneous xenotransplanted tumor model was established to detect tumorigenic function of TFPI2, and the underlying mechanism was evaluated by immunohistochemistry and western blot.
Results:
TFPI2 was down-regulated in breast cancer tissues and cell lines, and was associated with poor prognosis of patients diagnosed with breast cancer. Over-expression of TFPI2 inhibited cell viability, proliferation, migration and invasion of breast cancer cells. Mechanistically, Twist-related protein 1 (TWIST1) was negatively associated with TFPI2 in breast cancer patients, whose expression was decreased by TFPI2 over-expression or increased by TFPI2 knockdown. Moreover, TWIST1 could up-regulate integrin α5 expression. Functional assays indicated that the inhibition abilities of TFPI2 over-expression on breast cancer progression were reversed by TWIST1 over-expression. In vivo subcutaneous xenotransplanted tumor model also revealed that over-expression of TFPI2 could suppress breast tumor growth via down-regulation of TWIST1-mediated integrin α5 expression.
Conclusions:
TFPI2 suppressed breast cancer progression through inhibiting TWIST-integrin α5 pathway, providing a new potential therapeutic target for breast cancer treatment.
Insights
Tissue factor pathway inhibitor 2 (TFPI2) suppresses breast cancer progression by inhibiting the TWIST1-integrin α5 pathway. This discovery offers a potential new therapeutic target for breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tissue factor pathway inhibitor 2 (TFPI2) is implicated in various cancers and linked to poor breast cancer survival.
- The precise role and mechanism of TFPI2 in breast cancer progression require further elucidation.
Purpose of the Study:
- To investigate the effect of TFPI2 on breast cancer progression.
- To uncover the underlying molecular mechanisms of TFPI2 in breast cancer.
Main Methods:
- TFPI2 expression analyzed in breast cancer tissues and cell lines using qRT-PCR and immunohistochemistry.
- Cellular functions (viability, proliferation, migration, invasion) assessed via CCK8, colony formation, wound healing, and transwell assays.
- In vivo tumorigenic potential evaluated in a xenotransplanted tumor model, with mechanistic insights from western blot and immunohistochemistry.
Main Results:
- TFPI2 expression was reduced in breast cancer tissues and cell lines, correlating with poor patient prognosis.
- Overexpression of TFPI2 inhibited breast cancer cell viability, proliferation, migration, and invasion.
- TFPI2 suppressed tumor growth in vivo by downregulating the TWIST1-integrin α5 pathway.
Conclusions:
- TFPI2 inhibits breast cancer progression by suppressing the TWIST1-integrin α5 pathway.
- TFPI2 represents a potential therapeutic target for breast cancer treatment.
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