Introduction

Multifunctional adaptor proteins may have divergent actions in early versus late phases of cancer progression, playing both tumor-suppressing and tumor-promoting roles in a context-dependent manner. One such protein is the adaptor and caveolar coat protein caveolin-1, which is an essential structural constituent of plasma membrane caveolae (for a review, see [1,2]). The cellular localization of caveolin-1 is not limited to caveolae in all cells [3], and it exhibits diverse functions that go beyond its well-characterized role as a component of the caveolar coat (for a review, see [4]). Caveolin-1 was implicated in tumorigenesis because its expression is suppressed by oncogenic transformation, and little or no expression of caveolin-1 was initially found in various human tumors and cancer cell lines [5]. In addition, caveolin-1 has well-established growth-inhibitory properties, and it has been suggested to act as a tumor-suppressor protein [5]. However, a general tumor suppressor action cannot easily be reconciled with the fact that, in many other cancer cell lines and tumor specimens, the expression of caveolin-1 is high [6]. Furthermore, a positive correlation was often noted between the expression of caveolin-1 and the tumor cell grade and progression stage; in certain studies, the expression of caveolin-1 could be used to independently predict poor disease prognosis [6].

How can the divergent, cell type- and tumor stage-dependent changes in caveolin-1 be explained? Previous studies have indicated that in addition to its growth-inhibitory action, under certain circumstances caveolin-1 acts as a survival-promoting protein [7-14]. The differential expression of caveolin-1 in various tumor cells and specimens may thus be explained by the ability of caveolin-1 to exert both antiproliferative and pro-survival effects. It was previously hypothesized that, during the early stages of cancer progression (when rapid proliferation is essential for clonal expansion), expression of caveolin-1 is down-regulated, thus suppressing its growth-inhibitory actions. Conversely, during the late, advanced stages of the disease (when survival and stress resistance are paramount), expression of caveolin-1 is up-regulated and it plays a pro-survival role [6,15]. In the following sections we shall re-evaluate this hypothesis in view of recent evidence that relates the expression and function(s) of caveolin-1 to cancer progression and tumor cell survival.

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