Pancreatic　ductal　adenocarcinoma　(PDAC)　is　characterized　by　the　excessive　deposition　of　extracellular　matrix　(ECM),　which　is　thought　to　contribute　to　this　tumor＇s　malignant　behavior.　However,　the　detailed　mechanism　and　the　contribution　of　excessive　deposition　of　ECM　in　PDAC　progression　remain　unclear.　A　better　understanding　of　the　mechanism　involved　in　this　process　is　essential　for　the　design　of　new　effective　therapies.　In　this　study,　we　demonstrated　that　pancreatic　cancer　cells　exhibited　increased　proliferation　and　decreased　apoptosis　in　response　to　type　I　collagen.　In　addition,　PDAC　cells　exposed　to　type　I　collagen　lost　the　expression　of　E-cadherin　and　increased　expression　of　mesenchymal　markers,　including　N-cadherin　and　vimentin.　This　epithelial-　mesenchymal　transition　(EMT)　was　correlated　with　enhanced　cell　migration　and　invasiveness.　Knockdown　of　β1-integrin　abolished　the　effects　induced　by　type　I　collagen,　and　further　investigation　revealed　that　type　I　collagen　activates　β1-integrin　(marked　by　phosphorylation　of　β1　integrin　downstream　effectors,　focal　adhesion　kinase　[FAK],　AKT,　and　ERK)　accompanied　by　markedly　up-regulation　of　Gli-1,　a　component　of　the　Hedgehog　(HH)　pathway.　Knockdown　of　Gli-1　reversed　the　effects　of　type　I　collagen　on　PDAC　invasion　and　EMT.　These　results　suggest　that　there　is　cross-talk　between　the　β1-integrin　signaling　pathway　and　the　HH　pathway　in　pancreatic　cancer　and　that　activation　of　the　HH　pathway　plays　a　key　role　in　the　type　I　collagen-induced　effects　on　pancreatic　cancer.