title: CD44 regulates pancreatic cancer invasion through MT1-MMP.
abstract: Pancreatic cancer is one of the deadliest human malignancies due to its early metastatic spread and resistance to therapy. The mechanisms regulating pancreatic cancer metastasis are so far poorly understood. Here, using both in vitro and in vivo approaches, it is demonstrated that CD44, a transmembrane glycoprotein expressed on a subset of pancreatic cancer cells, is required for the induction of epithelial-mesenchymal transition (EMT) and the activation of an invasive program in pancreatic cancer. Mechanistically, the transcription factor Snail1 (SNAI1), a regulator of the EMT program, is a downstream target of CD44 in primary pancreatic cancer cells and regulates membrane bound metalloproteinase (MMP14/MT1-MMP) expression. In turn, MT1-MMP expression is required for pancreatic cancer invasion. Thus, these data establish the CD44-Snail-MMP axis as a key regulator of the EMT program and of invasion in pancreatic cancer.
  
  
  CONCLUSIONS
  This study sets the stage for CD44 and MT1-MMP as therapeutic targets in pancreatic cancer, for which small molecule or biologic inhibitors are available. Visual Overview: http://mcr.aacrjournals.org/content/early/2014/09/10/1541-7786.MCR-14-0076/F1.large.jpg.
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Kane
authors.affiliation: Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Collins
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Simeone
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan. Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan. marinapa@umich.edu ktnguyen74@yahoo.com.
authors.forename: Marina Pasca
authors.initials: MP
authors.lastname: di Magliano
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan. marinapa@umich.edu ktnguyen74@yahoo.com.
authors.forename: Kevin Tri
authors.initials: KT
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14