New Insights into the Molecular and Cellular Functions of Caveolin-1 in Skin Cancer.

摘要

As the main protein component of caveolae structures, Caveolin-1 has many functions, including an important role in the inhibition of cellular signal transduction events regulated through its scaffolding domain. Loss of Cav1 expression through mutation or misregulation has been implicated in the pathogenesis of several types of cancer, and Cav1 is a negative regulator of many malignant phenotypes, including proliferation, anchorage-independent growth, and invasion. Although previous studies suggest a role for Cav1 in cutaneous squamous cell carcinoma (cSCC) pathogenesis, little is known about the function of Cav1 in this malignancy. cSCC is the second most-commonly diagnosed malignancy among white populations, and its incidence is rising worldwide, making a better understanding of its pathogenesis essential for predicting disease outcome and developing better therapeutics. Herein, Cav1 is demonstrated to suppress benign tumorigenesis and inhibit epidermal proliferation both in primary keratinocytes in vitro and promoter-treated epidermis in vivo. In addition, Cav1 functions to suppress proliferation, invasion, and metastasis in a murine model of cSCC, attributed in part to its ability to inhibit signaling along the Ras/Erk/AP-1 pathway. Furthermore, decreased Cav1 expression correlates with increasing tumor grade in human tumors. This work provides evidence that Cav1 functions in both the promotion and progression stages of cSCC development, and is therefore a valid target for therapeutic intervention. In addition, the contribution of Cav1 to metastatic progression illustrates its potential value as a biomarker to predict aggressive tumor behavior. Although further work is needed to elucidate the mechanisms of Cav1 action in skin cancer, the research discussed herein makes it evident that Cav1 is a worthwhile avenue to pursue in cSCC research.