Abstract
Caveolin-1 (CAV1) is commonly considered to function as a cell surface protein, for instance in the genesis of caveolae. Nonetheless, it is also present in many intracellular organelles and compartments. The contributions of these intracellular pools to CAV1 function are generally less well understood, and this is also the case in the context of cancer. This review will summarize literature available on the role of CAV1 in cancer, highlighting particularly our understanding of the canonical (CAV1 in the plasma membrane) and non-canonical pathways (CAV1 in organelles and exosomes) linked to the dual role of the protein as a tumor suppressor and promoter of metastasis. With this in mind, we will focus on recently emerging concepts linking CAV1 function to the regulation of intracellular organelle communication within the same cell where CAV1 is expressed. However, we now know that CAV1 can be released from cells in exosomes and generate systemic effects. Thus, we will also elaborate on how CAV1 participates in intracellular communication between organelles as well as signaling between cells (non-canonical pathways) in cancer.
Highlights
Caveolin-1 (CAV1) is a small, oligomeric scaffolding protein, typically required to generate membrane curvature in structures, such as caveolae [123, 174]
The caveola formation observed upon PTRF/cavin1 overexpression correlates with a reduction in migration that is associated with CAV1 accumulation in caveolae at the cell rear, increases in E-cadherin, and decreases in vimentin and metalloprotease 9 together with Rac-1 depolarization, all processes related to the inhibition of epithelial-mesenchymal transition (EMT)
Another report shows that the treatment of triple negative breast cancer cells with bitter melon extract reduces the accumulation of esterified cholesterol, acetyl-CoA:cholesterol acyltransferase 1 (ACAT1), and LDL receptor expression, thereby reducing tumor growth in mammospheres implanted into mice [152]
Summary
Caveolin-1 (CAV1) is a small, oligomeric scaffolding protein, typically required to generate membrane curvature in structures, such as caveolae [123, 174]. The CSD regulates Ca2+ influx into cells by interacting with and modulating the activity of certain ion channels, such as TRPC1 [117, 160], thereby leading to the alteration of cellular processes, including cell proliferation [25] and tumor invasion [117] This domain is suggested to be crucial in controlling cell migration, possibly via STAT3, and cell cycle progression in several cancer cell lines [117]. The CSD is buried in the membrane and inaccessible for the interaction with cytoplasmic proteins [5] This data points towards the relevance of other mechanisms through which CAV1 regulates signaling events, such as those previously mentioned involving alterations in the lipid domain organization or via interactions mediated by segments of the protein that are phosphorylated. Here, we will review in detail the literature available on the role of CAV1 in cancer and the canonical and non-canonical functions of the proteins associated with CAV1 at the plasma membrane and in other subcellular localizations, respectively
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