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WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma
Hsiao-Chi Tsai1, Huey-En Tzeng2,3, Chun-Yin Huang3,4
1Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Cell Death & Disease
|April 14, 2017
Summary
WNT1-inducible signaling pathway protein-1 (WISP-1) promotes osteosarcoma angiogenesis by increasing vascular endothelial growth factor-A (VEGF-A) expression via FAK/JNK/HIF-1α pathways and downregulating miR-381. WISP-1 is a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma angiogenesis, regulated by vascular endothelial growth factor-A (VEGF-A), is crucial in disease progression.
- WNT1-inducible signaling pathway protein-1 (WISP-1) is implicated in various cancers, but its role in osteosarcoma angiogenesis is unclear.
Purpose of the Study:
- To investigate the role of WISP-1 in osteosarcoma angiogenesis.
- To elucidate the molecular mechanisms underlying WISP-1-mediated angiogenesis in osteosarcoma.
Main Methods:
- Correlation analysis of WISP-1 and VEGF-A expression in human osteosarcoma.
- In vitro studies using osteosarcoma cells and human endothelial progenitor cells (EPCs).
- Investigated signaling pathways (FAK, JNK, HIF-1α) and microRNA-381 (miR-381) involvement using inhibitors and siRNA.
Main Results:
- Positive correlation observed between WISP-1 and VEGF-A expression in osteosarcoma.
- WISP-1 significantly promoted VEGF-A expression, enhancing EPC migration and tube formation.
- WISP-1 activated FAK, JNK, and HIF-1α pathways, and down-regulated miR-381, which were critical for its pro-angiogenic effects.
Conclusions:
- WISP-1 promotes osteosarcoma angiogenesis by upregulating VEGF-A through the FAK/JNK/HIF-1α signaling cascade and downregulating miR-381.
- WISP-1 represents a potential therapeutic target for inhibiting osteosarcoma angiogenesis.