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Xu XZ , Garcia MV , Li TY , Khor LY , Gajapathy RS , Spittle C , Weed S , Lessin SR , Wu H
Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression
Mod Pathol. 2010 Feb;23(2) :187-96
PMID: 19898426 PMCID: PMC2827925
AbstractCortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to study the role of cortactin in melanocytic tumor progression using immunohistochemistry on human tissues. The results reveal quantitative differences between benign and malignant lesions. Significantly higher cortactin expression is found in melanomas than in nevi (P<0.0001), with levels greater in metastatic than in invasive melanomas (P<0.05). Qualitatively, tumor tissues often show aberrant cortactin localization at the cell periphery, corresponding to its colocalization with filamentous actin in cell cortex of cultured melanoma cells. This suggests an additional level of protein dysregulation. Furthermore, in patients with metastatic disease, high-level cortactin expression correlates with poor disease-specific survival. Our data, in conjunction with outcome data on several other types of human cancers and experimental data from melanoma cell lines, supports a potential role of aberrant cortactin expression in melanoma tumor progression and a rational for targeting key elements of actin-signaling pathway for developmental therapeutics in melanomas.
NotesXu, Xu-Zhi Garcia, Marileila Varella Li, Tian-yu Khor, Li-Yan Gajapathy, R Sujatha Spittle, Cindy Weed, Scott Lessin, Stuart R Wu, Hong P20 RR016440-096547/RR/NCRR NIH HHS/United States P20 RR16440/RR/NCRR NIH HHS/United States R01 DE014578-06/DE/NIDCR NIH HHS/United States R01DE014578/DE/NIDCR NIH HHS/United States Research Support, N.I.H., Extramural United States Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Mod Pathol. 2010 Feb;23(2):187-96. Epub 2009 Nov 6.