title: Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells.
abstract: Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease. The aim of this study was to investigate the role of myeloid cell nuclear factor-κB in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 (rela(Δ-/-)) to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell tumors in wild-type mice. In CS-exposed rela(Δ-/-) mice, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways, including the Wnt/β-catenin pathway. In conclusion, myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth and has a role in the activation of Wnt/β-catenin signaling in tumor cells.
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Beisswenger
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hellberg
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Zakharkina
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Voss
authors.affiliation: Pulmonary Division, Department of Medicine A, Münster University Hospital, Münster, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wiewrodt
authors.affiliation: Department of Pathology, Saarland University Hospital, Homburg, Germany.
authors.forename: R M
authors.initials: RM
authors.lastname: Bohle
authors.affiliation: Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany.
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
authors.affiliation: Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
authors.forename: R M
authors.initials: RM
authors.lastname: Schmid
authors.affiliation: Center for Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Stöckel
authors.affiliation: Center for Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: H-P
authors.initials: HP
authors.lastname: Lenhof
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bals
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism*; D009368:Neoplasm Transplantation; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects; D051996:Transcription Factor RelA / Q000502:physiology*; D059467:Transcriptome; D047368:Tumor Burden; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3