Caveolin‐1: an ambiguous partner in cell signalling and cancer

Abstract

Caveolae are small plasma membrane invaginations that have been implicated in a variety of functions including transcytosis, potocytosis and cholesterol transport and signal transduction. The major protein component of this compartment is a family of proteins called caveolins. Experimental data obtained in knockout mice have provided unequivocal evidence for a requirement of caveolins to generate morphologically detectable caveolae structures. However, expression of caveolins is not sufficient per seto assure the presence of these structures. With respect to other roles attributed to caveolins in the regulation of cellular function, insights are even less clear. Here we will consider, more specifically, the data concerning the ambiguous roles ascribed to caveolin-1 in signal transduction and cancer. In particular, evidence indicating that caveolin-1 function is cell context dependent will be discussed.

The Caveolin-1 Connection to Cell Death and Survival

“…presence of the protein is associated with more aggressive tumor behavior. For additional information in this respect, the interested reader may wish to consider previous reviews where such ideas have been discussed extensively [11,61]. A corollary to this concept is that Caveolin-1 function as a tumor suppressor is linked to events favoring cell death, while more aggressive tumor behavior is likely to be associated with Caveolin-1-dependent mechanisms that favor cell survival.…”

“…Most notably, Caveolin-1 contains a tyrosine residue in position 14 that is phosphorylated in response to a large number of different stimuli. Often, but not always, non-receptor tyrosine kinases of the Src family are involved and phosphorylation is triggered as part of a so-called stress response [11]. The importance of Caveolin-1 in this context is underscored by the fact that Caveolin-1 knock-out mice display a remarkably reduced ability to regenerate specific tissues like the liver and also a dramatic decrease in life span [17][18].…”

“…Generally, however, loss of Caveolin-1 expression in tumors is now thought to occur via epigenetic mechanisms, including DNA methylation, rather than mutational changes. A detailed discussion of such mechanisms, as well as transcriptional pathways controlling Caveolin-1 expression can be found elsewhere [11]. However, a P132L mutation in Caveolin-1 was detected in 16% of human breast cancer patients analyzed in one study [37].…”

“…Conversely, at later stages of tumor progression, Caveolin-1 has been shown to promote tumor cell migration, multi-drug resistance and, therefore its presence correlates with poor patient prognosis. Whether Caveolin-1 elicits one or the other response seems dependent on the tumor type and the cellular context [11,19]. In this review, we will focus predominantly on discussing the ability of Caveolin-1 to modulate processes associated with cell death and survival.…”

Membrane lipids in invadopodia and podosomes: Key structures for cancer invasion and metastasis

“…Although further studies are needed to elucidate the precise functions of caveolin-1 in invadopodia formation, these findings imply that caveolin-1 plays multiple roles in the trafficking of invadopodia components. Clinical studies showed that the increased expression of caveolin-1 is correlated with the presence of metastasis and poor prognosis in several human cancers [28,29]. Taken together, blocking the functions of lipid rafts and caveolin-1 should be an approach to targeting invadopodia-mediated cancer cell invasion.…”