Cutting Edge Therapies for Cancer in the 21st Century

Role of Caveolin-1 in Cancer and Therapeutic Implications

Author(s): Gloria Bonuccelli, Philippe G. Frank and Michael P. Lisanti

Pp: 3-27 (25)

Doi: 10.2174/9781608058808114010004

* (Excluding Mailing and Handling)

Abstract

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.

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