Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression.
Cortactin 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.
Xu
Xu-Zhi
XZ
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Garcia
Marileila Varella
MV
Li
Tian-yu
TY
Khor
Li-Yan
LY
Gajapathy
R Sujatha
RS
Spittle
Cindy
C
Weed
Scott
S
Lessin
Stuart R
SR
Wu
Hong
H
D014408:Biomarkers, Tumor / Q000032:analysis*; D051356:Cortactin / Q000096:biosynthesis*; D003599:Cytoskeleton / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009506:Nevus / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D051356:Cortactin