Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma: Implications for tumor progression and clinical outcome

Agnieszka K. Witkiewicz, Katherine H. Nguyen, Abhijit Dasgupta, Eugene P. Kennedy, Charles J. Yeo, Michael P. Lisanti, Jonathan R. Brody

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Pancreatic cancer is a devastating disease that afflicts over 35,000 Americans every year. Since therapeutic options are limited, understanding the molecular aspects of this disease is critical for moving towards targeted treatment of this aggressive form of cancer. Caveolin-1 (Cav-1) and fatty acid synthase (FASN) are two proteins that have been shown to be dysregulated in a number of cancers. Functionally these proteins have been shown to be involved in the process of tumorigenesis. We thus surveyed the expression of both these critical proteins in a series of pancreatic precancerous lesions (pancreatic intraepithelial neoplasia, PanIN) and pancreatic cancers. Cav-1 and FASN expression correlated predominantly with clinical characteristics, such as histologic grade and advanced tumor stage (e.g., high Cav-1 and FASN expression correlated with poor differentiation status) and a significant survival advantage was found in patients with low co-expressing FASN and Cav-1 tumors. Cav-1 and FASN expression was absent in PanIN lesions and the normal ducts and acini. Of note, Cav-1 expression was detected in the fibroblasts of the desmoplastic pancreatic cancer stroma, but not in stromal cells of the normal pancreas. Mechanistically, these data support the notion that these proteins are co-regulated either directly or indirectly by another factor. Importantly, the co-expression of these proteins significantly correlates with clinical features and survival status of pancreatic cancer patients. Thus, Cav-1 and FASN may functionally cooperate in the process of pancreatic tumorigenesis, and as such, may be good candidate prognostic markers and targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)3021-3025
Number of pages5
JournalCell Cycle
Volume7
Issue number19
StatePublished - Oct 1 2008

Fingerprint

Caveolin 1
Fatty Acid Synthases
Adenocarcinoma
Pancreatic Neoplasms
Neoplasms
Proteins
Carcinogenesis
Survival
Stromal Cells
Pancreas
Therapeutics
Fibroblasts

Keywords

  • Caveolin-1
  • Fatty acid synthase
  • Pancreatic cancer
  • Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Witkiewicz, A. K., Nguyen, K. H., Dasgupta, A., Kennedy, E. P., Yeo, C. J., Lisanti, M. P., & Brody, J. R. (2008). Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma: Implications for tumor progression and clinical outcome. Cell Cycle, 7(19), 3021-3025.

Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma : Implications for tumor progression and clinical outcome. / Witkiewicz, Agnieszka K.; Nguyen, Katherine H.; Dasgupta, Abhijit; Kennedy, Eugene P.; Yeo, Charles J.; Lisanti, Michael P.; Brody, Jonathan R.

In: Cell Cycle, Vol. 7, No. 19, 01.10.2008, p. 3021-3025.

Research output: Contribution to journalArticle

Witkiewicz, AK, Nguyen, KH, Dasgupta, A, Kennedy, EP, Yeo, CJ, Lisanti, MP & Brody, JR 2008, 'Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma: Implications for tumor progression and clinical outcome', Cell Cycle, vol. 7, no. 19, pp. 3021-3025.
Witkiewicz, Agnieszka K. ; Nguyen, Katherine H. ; Dasgupta, Abhijit ; Kennedy, Eugene P. ; Yeo, Charles J. ; Lisanti, Michael P. ; Brody, Jonathan R. / Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma : Implications for tumor progression and clinical outcome. In: Cell Cycle. 2008 ; Vol. 7, No. 19. pp. 3021-3025.
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