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Published on: November 23, 2014
ING4 regulates JWA in angiogenesis and their prognostic value in melanoma patients
11] Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada [2] Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.
Background:
We previously showed that inhibitor of growth family member 4 (ING4) inhibits melanoma angiogenesis, and JWA suppresses the metastasis of melanoma cells. As angiogenesis is essential for tumour metastasis, further investigation of the function of ING4 and JWA in melanoma angiogenesis is needed, and their prognostic value are of great interest.
Methods:
Western blot, tube-formation assays and luciferase assays were used to investigate the correlation between ING4 and JWA in melanoma angiogenesis. JWA and integrin-linked kinase (ILK) expression was determined on a tissue microarray constructed from 175 biopsies.
Results:
ING4 promoted JWA expression by activating JWA promoter. Furthermore, the regulation of growth and tube formation of endothelial cells by ING4 was partially JWA dependent. Also, ING4 inhibited the ILK-induced angiogenesis signalling pathway via JWA. Moreover, reduced JWA, or increased ILK, expression was closely associated with 5-year disease-specific survival of melanoma patients (P=0.001 and 0.007, respectively). There was also a positive correlation between ING4 and JWA yet a negative correlation between ING4 and ILK. Importantly, their concomitant expressions were significantly related to 5-year survival of melanoma patients (P=0.002 and 0.003, respectively).
Conclusion:
JWA has an important role in ING4-regulated melanoma angiogenesis, and ING4/JWA/ILK are promising prognostic markers and may be used as anti-angiogenic therapeutic targets for melanoma.
Insights
Inhibitor of growth family member 4 (ING4) and JWA play key roles in melanoma angiogenesis. Their combined expression levels serve as important prognostic markers for melanoma patient survival and potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Inhibitor of growth family member 4 (ING4) inhibits melanoma angiogenesis.
- JWA suppresses melanoma cell metastasis.
- Angiogenesis is critical for tumor metastasis, necessitating further study of ING4 and JWA roles and prognostic value.
Purpose of the Study:
- Investigate the correlation between ING4 and JWA in melanoma angiogenesis.
- Determine the prognostic value of ING4, JWA, and integrin-linked kinase (ILK) in melanoma patients.
Main Methods:
- Western blot, tube-formation assays, and luciferase assays were employed.
- JWA and ILK expression analyzed via tissue microarray in 175 melanoma biopsies.
Main Results:
- ING4 promotes JWA expression and partially mediates ING4's regulation of endothelial cell growth and tube formation.
- ING4 inhibits ILK-induced angiogenesis via JWA.
- Reduced JWA or increased ILK expression correlates with decreased 5-year survival.
- ING4/JWA/ILK expression levels are significant predictors of 5-year melanoma survival.
Conclusions:
- JWA is crucial in ING4-regulated melanoma angiogenesis.
- ING4, JWA, and ILK are promising prognostic markers for melanoma.
- The ING4/JWA/ILK pathway presents potential anti-angiogenic therapeutic targets for melanoma.
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