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Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells.
Invest Ophthalmol Vis Sci. 2008 Feb; 49(2):497-504.IO

Abstract

PURPOSE

Uveal melanoma is the most common primary intraocular malignancy in adult humans. Unlike cutaneous melanoma, uveal melanoma disseminates preferentially to the liver through the hematogenous system. To date, the mechanism underlying this metastatic homing is largely unknown. This study investigated the effect of hepatocyte growth factor (HGF)-triggered signaling pathways to identify the role of HGF and its downstream effectors in inducing the migration of uveal melanoma cells.

METHODS

Migration of uveal melanoma cells was measured by in vitro wound healing and transwell migration assays. The expression and translocation of c-Met were detected using indirect immunofluorescence. The activation of extracellular signal-regulated kinase (ERK)1/2 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathways was analyzed using specific antibodies against phospho-ERK1/2 and phospho-Akt. The impact of HGF treatment on the expression of cell adhesion molecules was measured using Western blotting.

RESULTS

HGF was found to enhance cell migration, and that HGF-induced migration depends on PI3K/Akt pathway. The activation of PI3K/Akt pathway induced by the HGF/c-Met axis is involved in the downregulation of cell adhesion molecules E-cadherin and beta-catenin, contributing to the attenuation of cell-cell adhesion and promoting the enhanced motility and migration of uveal melanoma cells. On HGF stimulation, receptor c-Met is translocated to the nucleus in a ligand-dependent manner, suggesting that c-Met may modulate the expression of genes involved in melanoma cell migration.

CONCLUSIONS

Data from this study directly linked the central PI3K/Akt pathway to uveal melanoma migration and pointed to new avenues for therapeutic intervention in hepatic metastasis.

Authors+Show Affiliations

School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18234991

Citation

Ye, Mao, et al. "Involvement of PI3K/Akt Signaling Pathway in Hepatocyte Growth Factor-induced Migration of Uveal Melanoma Cells." Investigative Ophthalmology & Visual Science, vol. 49, no. 2, 2008, pp. 497-504.
Ye M, Hu D, Tu L, et al. Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells. Invest Ophthalmol Vis Sci. 2008;49(2):497-504.
Ye, M., Hu, D., Tu, L., Zhou, X., Lu, F., Wen, B., Wu, W., Lin, Y., Zhou, Z., & Qu, J. (2008). Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells. Investigative Ophthalmology & Visual Science, 49(2), 497-504. https://doi.org/10.1167/iovs.07-0975
Ye M, et al. Involvement of PI3K/Akt Signaling Pathway in Hepatocyte Growth Factor-induced Migration of Uveal Melanoma Cells. Invest Ophthalmol Vis Sci. 2008;49(2):497-504. PubMed PMID: 18234991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells. AU - Ye,Mao, AU - Hu,Danning, AU - Tu,Lili, AU - Zhou,Xiangtian, AU - Lu,Fan, AU - Wen,Bin, AU - Wu,Wencan, AU - Lin,Yi, AU - Zhou,Zhonglou, AU - Qu,Jia, PY - 2008/2/1/pubmed PY - 2008/3/14/medline PY - 2008/2/1/entrez SP - 497 EP - 504 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 49 IS - 2 N2 - PURPOSE: Uveal melanoma is the most common primary intraocular malignancy in adult humans. Unlike cutaneous melanoma, uveal melanoma disseminates preferentially to the liver through the hematogenous system. To date, the mechanism underlying this metastatic homing is largely unknown. This study investigated the effect of hepatocyte growth factor (HGF)-triggered signaling pathways to identify the role of HGF and its downstream effectors in inducing the migration of uveal melanoma cells. METHODS: Migration of uveal melanoma cells was measured by in vitro wound healing and transwell migration assays. The expression and translocation of c-Met were detected using indirect immunofluorescence. The activation of extracellular signal-regulated kinase (ERK)1/2 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathways was analyzed using specific antibodies against phospho-ERK1/2 and phospho-Akt. The impact of HGF treatment on the expression of cell adhesion molecules was measured using Western blotting. RESULTS: HGF was found to enhance cell migration, and that HGF-induced migration depends on PI3K/Akt pathway. The activation of PI3K/Akt pathway induced by the HGF/c-Met axis is involved in the downregulation of cell adhesion molecules E-cadherin and beta-catenin, contributing to the attenuation of cell-cell adhesion and promoting the enhanced motility and migration of uveal melanoma cells. On HGF stimulation, receptor c-Met is translocated to the nucleus in a ligand-dependent manner, suggesting that c-Met may modulate the expression of genes involved in melanoma cell migration. CONCLUSIONS: Data from this study directly linked the central PI3K/Akt pathway to uveal melanoma migration and pointed to new avenues for therapeutic intervention in hepatic metastasis. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/18234991/Involvement_of_PI3K/Akt_signaling_pathway_in_hepatocyte_growth_factor_induced_migration_of_uveal_melanoma_cells_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.07-0975 DB - PRIME DP - Unbound Medicine ER -