title: CD44 promotes Kras-dependent lung adenocarcinoma.
abstract: Kras-induced non-small-cell lung adenocarcinoma is the major subtype of lung cancers and is associated with poor prognosis. Using a lung cancer mouse model that expresses a cre-mediated KrasG12D mutant, we identified a critical role for the cell surface molecule CD44 in mediating cell proliferation downstream of oncogenic Kras signaling. The deletion of CD44 attenuates lung adenocarcinoma formation and prolongs the survival of these mice. Mechanistically, CD44 is required for the activation of Kras-mediated signaling through the mitogen-activated protein kinase (MAPK) pathway and thus promotes tumor cell proliferation. Together, these results reveal an unrecognized role for CD44 in oncogenic Kras-induced lung adenocarcinoma and suggest that targeting CD44 could be an effective strategy for halting Kras-dependent carcinomas.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.forename: M S
authors.initials: MS
authors.lastname: Damerow
authors.forename: P
authors.initials: P
authors.lastname: Stern
authors.forename: A H
authors.initials: AH
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Sweet-Cordero
authors.forename: K
authors.initials: K
authors.lastname: Siziopikou
authors.forename: J R
authors.initials: JR
authors.lastname: Neilson
authors.forename: P A
authors.initials: PA
authors.lastname: Sharp
authors.forename: C
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D020928:Mitogen-Activated Protein Kinases; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)