Caveolae are flask-shaped plasma membrane invaginations that represent a
subset of the well-known lipid raft. These organelles are characterized by the presence of
the caveolin-1 (Cav-1) protein that plays an important role in the regulation of several
signal transduction pathways. More than ten years ago, in vitro experiments showed that
downregulation of Cav-1 drives cell transformation and hyperactivation of the Ras-p42/44
MAP kinase cascade. In addition, it was shown that Cav-1 functions as a repressor of
cyclin D1, possibly explaining its tumor suppressor activity in cultured cells. Later on, in
vivo experiments showed that Cav-1 was involved in tumor development. In particular, the
absence of Cav-1 in mouse skin increased the susceptibility to carcinogen-induced
epidermal hyperplasia and tumor formation. Moreover, loss of Cav-1 expression caused the
development of dysplastic mammary lesions in tumor-prone transgenic mice where cyclin
D1 expression levels were dramatically elevated. These studies were the first in vivo
demonstrations showing that caveolin-1 could function as a tumor suppressor gene.
However, other investigators have shown that certain cancer cells show up-regulation of
caveolin-1 that results in more metastatic and aggressive tumor like in bladder, thyroid, and
prostate carcinomas. Taken together, these data suggest that Cav-1 is implicated in both
tumor suppression and oncogenesis.
Keywords: Caveolae, caveolin-1, breast cancer, prostate cancer, melanoma,
metalloproteins, MMP-2, MMP-9, estrogen receptor, P132L, EGFR, Her2/Neu,
PDGF receptor tyrosine kinases, Ras, MAP kinase, PI-3-kinase, Warburg effect,
Reverse Warburg effect.
