1. ¹Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA
2. ²Department of Medicine/Medical Oncology, University of Colorado Health Sciences Center, Denver, CO, USA
3. ³Facility of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA, USA
4. ⁴Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
5. ⁵Facility of Biomarkers, Fox Chase Cancer Center, Philadelphia, PA, USA
6. ⁶Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University
7. ⁷Department of Medicine, Fox Chase Cancer Center, Philadelphia, PA, USA

Correspondence: Dr H Wu, Department of Pathology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. E-mail: hong.wu@fccc.edu

Received 16 March 2009; Revised 19 July 2009; Accepted 20 July 2009; Published online 6 November 2009.

Abstract

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.