| Sumario: | Caveolin-1 is a member of the caveolin family of proteins that are implicated in caveolae morphogenesis, cholesterol homeostasis, and regulation of a plethora of signaling pathways. Moreover, this isoform, in particular, is suggested to function as a regulator of tumor development and progression. Since caveolin-1 inhibits many signaling pathways that favor cell proliferation and reduce cell death, caveolin-1 was ascribed the role of a tumor suppressor. Insights from studies in knock-out mice favor this interpretation, since caveolin-1 absence augments “tumor susceptibility,” that is tumor development in specific experimental settings occurs more readily in these animals. However, an alternative, opposite view is also provided by data available in the literature, indicating that caveolin-1 promotes tumorigenesis and is associated with phenomena like multidrug resistance, enhanced invasiveness, and metastasis. Indeed, in certain human cancers, caveolin-1 expression correlates with poor patient prognosis and decreased survival. Hence, the role that caveolin-1 plays in cancer is currently a matter of intense debate. Here, the discussion will focus on this “ambiguity” of caveolin-1 function in the context of colon cancer. Alterations in canonical Wnt signaling and ?-catenin-Tcf/Lef-dependent transcription are frequently associated with the development of this disease. Evidence indicating how the presence of caveolin-1 inhibits signaling through this pathway, as well as how the ability of caveolin-1 to do so is modulated both by intracellular and extracellular conditions will be discussed. Finally, a model based on the events described in colon cancer cells will be developed to summarize events considered relevant to caveolin-1 function as a “conditional” tumor suppressor.
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