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Caveolin-1 and Pancreatic Ductal Adenocarcinoma

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Caveolins in Cancer Pathogenesis, Prevention and Therapy

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Pancreatic ductal adenocarcinoma (PDA) is a devastating disease because the annual incidence nearly equals the annual mortality. Landmark studies have identified the key genetic alterations that play a role in PDA tumorigenesis. However, recent work has underscored the importance of the pancreatic tumor microenvironment and other proteins that may be alternatively regulated in PDA cells. Caveolin (Cav-1), an integral membrane protein that plays a role in endo and exocytosis and intracellular signal transduction, is an example of a protein that appears to play a central role in PDA tumorigenesis. Cav-1 has been shown to have both oncogenic and tumor suppressor properties in lung and prostate cancers depending on the experimental setting. PDA models have demonstrated similar roles for Cav-1. For example, Cav-1 contributes to anchorage independent cell survival by its interaction with a cell surface protein, carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which leads to PDA tumor growth and aggressiveness through the regulation of matrix metalloproteinases (MMPs). Conversely, Cav-1 can inhibit PDA tumor growth and development by regulating the EGFR-mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, Cav-1 suppresses progression of PDA by inhibiting Rho GTPases which are small monomeric molecules that are typically involved in actin cytoskeleton rearrangement during cellular migration. Clinically, Cav-1 expression, as a biomarker, correlates with patient survival, pathologic features, and fatty acid synthase (FASN) expression. Ongoing studies will elucidate the intricate way in which Cav-1 facilitates the pancreatic tumorigenesis process (including its role in the reverse Warburg effect in the PDA environment) as well as treatment interventions (radioresistance) for this devastating disease. These studies will aid us in better understanding the meaning of Cav-1 expression levels in pancreatic tumor cells and its microenvironment.

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Author information

Authors and Affiliations

  1. Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    David W. Rittenhouse, Oeendree Mukherjee, Nathan G. Richards, Charles J. Yeo, Agnieszka K. Witkiewicz & Jonathan R. Brody

  2. Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA

    Agnieszka K. Witkiewicz & Jonathan R. Brody

Authors
  1. David W. Rittenhouse
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  2. Oeendree Mukherjee
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  3. Nathan G. Richards
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  4. Charles J. Yeo
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  5. Agnieszka K. Witkiewicz
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  6. Jonathan R. Brody
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Corresponding author

Correspondence to Jonathan R. Brody .

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Editors and Affiliations

  1. Kimmel Cancer Center, Thomas Jefferson University, S. 10th Street 233, Philadelphia, 19107, Pennsylvania, USA

    Isabelle Mercier

  2. Bluemle Bldg, Rm 939, Department of Stem Cell Biology and Rege, Thomas Jefferson University, S. 10th Street 233, Philadelphia, 19107, Pennsylvania, USA

    Jean-François Jasmin

  3. Kimmel Cancer Center, Thomas Jefferson University, S. 10th Street 233, Philadelphia, 19107, Pennsylvania, USA

    Michael P. Lisanti

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Rittenhouse, D.W., Mukherjee, O., Richards, N.G., Yeo, C.J., Witkiewicz, A.K., Brody, J.R. (2012). Caveolin-1 and Pancreatic Ductal Adenocarcinoma. In: Mercier, I., Jasmin, JF., Lisanti, M. (eds) Caveolins in Cancer Pathogenesis, Prevention and Therapy. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1001-0_3

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  • DOI: https://doi.org/10.1007/978-1-4614-1001-0_3

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