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FOXL1, a Novel Candidate Tumor Suppressor, Inhibits Tumor Aggressiveness and Predicts Outcome in Human Pancreatic Cancer

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45




  • G Zhang
  • PJ He
  • J Gaedcke
  • BM Ghadimi
  • T Ried
  • HG Yfantis
  • DH Lee
  • N Hanna
  • HR Alexander
  • SP Hussain


The Forkhead Box L1 (FOXL1) transcription factor regulates epithelial proliferation and development of gastrointestinal track, and has been implicated in gastrointestinal tumorigenesis in mouse models. However, the role of FOXL1 in pancreatic cancer development and progression remains to be elucidated. Here, we report that a higher FOXL1 expression is significantly associated with better clinical outcome in human pancreatic ductal adenocarcinoma (PDAC). We demonstrate that over-expression of FOXL1 induces apoptosis and inhibits proliferation and invasion in pancreatic cancer cells, whereas silencing of FOXL1 by siRNA inhibits apoptosis and enhances tumor cell growth and invasion. We show that FOXL1 promotes apoptosis partly through the induction of TNF-related apoptosis-inducing ligand (TRAIL) in pancreatic cancer cells. Furthermore, FOXL1 suppresses the transcription of zinc finger E-box-binding homeobox 1 (ZEB1), an activator of epithelial mesenchymal transition (EMT). The negative regulation of ZEB1 contributes to the inhibitory effect of FOXL1 on tumor invasion. Taken together, our findings suggest that FOXL1 is a candidate predictor of outcome in patients with resected PDAC and may play a role in suppressing pancreatic tumor progression.

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