Cavin-1 is essential for the tumor-promoting effect of caveolin-1 and enhances its prognostic potency in pancreatic cancer

  • Liu L
  • Xu H
  • Wang W
 et al. 
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Abstract

Caveolin-1 exhibits a stage-dependent, functional fluctuation during pancreatic cancer development, but the underlying mechanisms remain unclear. Here, we report that cavin-1, a structural protein of caveolae, modulates the oncogenic function of caveolin-1 and cooperates with caveolin-1 to enhance pancreatic cancer aggressiveness. Cavin-1 expression is associated with caveolin-1 in pancreatic cancer tissue samples and cell lines, and predicts the metastatic potential of pancreatic cancer. Interactome analyses further revealed the physical interaction of cavin-1 and caveolin-1 and their colocalization in pancreatic cancer cells. Cavin-1 stabilizes caveolin-1 expression or activity by inhibiting its internalization and subsequent lysosomal degradation. More in-depth functional experiments showed that caveolin-1-enhanced aggressiveness of pancreatic cancer cells is dependent on the presence of cavin-1. In contrast, cavin-1 depletion inhibited the invasion and metastasis of pancreatic cancer cells, which could not be restored by caveolin-1-rescue construct. Tissue microarray analyses in two independent clinic cohorts also supported the augment of cavin-1 on the prognostic potency of caveolin-1, and showed that combination of cavin-1 with caveolin-1 predicted worse survival in pancreatic cancer patients. Of note, the phenotypes because of cavin-1 could not be achieved by other cavins such as cavin-2, and the tumor-promoting role of cavin-1 in pancreatic cancer was found to be largely dependent on caveolin-1 expression, which highlights the critical role of cavin-1/caveoin-1 in pancreatic cancer progression, and suggests that the interruption of cavin-1/caveolin-1 interaction is a promising therapeutic strategy for pancreatic cancer.Oncogene advance online publication, 17 June 2013; doi:10.1038/onc.2013.223.

Author-supplied keywords

  • Cavin-1
  • caveolin-1
  • metastatic potential
  • pancreatic cancer
  • prognostic potency

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Authors

  • L. Liu

  • H. X. Xu

  • W. Q. Wang

  • C. T. Wu

  • T. Chen

  • Y. Qin

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