TGF? can stimulate the p(38)/?-catenin/PPAR? signaling pathway to promote the EMT, invasion and migration of non-small cell lung cancer (H460 cells).
Signaling pathway(s) responsible for transforming growth factor ? (TGF?)-induced epithelial mesenchymal transition (EMT), invasion and migration of H460 cells (non-small cell lung cancer/NSCLC) was identified in the study. The results showed that TGF?-induced p(38)/?-catenin/PPAR? signaling pathway played a critical role in the promotion of EMT, invasion and migration of H460 ... cells. All these pathological outcomes attributed to PPAR?-increased expression of p-EGFR, p-c-MET and Vimentin and the decrease of E-cadherin. Transforming growth factor ? and p(38)-induced ?-catenin not only stimulated the expression of PPAR? but also physically interacted with it. Blocking the ligand binding domain of PPAR? (with GW9662) could significantly interfere the binding between PPAR? and ?-catenin, and interrupt the nuclear infiltration of both factors. These findings suggested that ?-catenin was an upstream regulator and a ligand of PPAR?, and the binding between these two molecules was critical for their nuclear infiltration. Transforming growth factor ?-induced tumor invasion and migration was also seen in U373 cells (brain glioma, with high inducible PPAR?) in a PPAR?-dependent manner, but not in CH27 cells (squamous NSCLC, with low PPAR?). PPAR? shRNA, GW9662, JW67 and 2,4-diaminoquinazoline were all revealed to have important values in the control of the intrinsic and TGF?-induced EMT, tumor invasion and migration of H460 cells. The results further suggested that PPAR? and ?-catenin may be the potential markers for the early diagnosis and/or treatment of metastatic tumors.
Mesh Terms:
Apoptosis, Blotting, Western, Carcinoma, Non-Small-Cell Lung, Cell Adhesion, Cell Cycle, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Fluorescent Antibody Technique, Humans, Immunoprecipitation, Lung Neoplasms, PPAR gamma, RNA, Small Interfering, Signal Transduction, Transforming Growth Factor beta, Tumor Cells, Cultured, beta Catenin, p38 Mitogen-Activated Protein Kinases
Apoptosis, Blotting, Western, Carcinoma, Non-Small-Cell Lung, Cell Adhesion, Cell Cycle, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Fluorescent Antibody Technique, Humans, Immunoprecipitation, Lung Neoplasms, PPAR gamma, RNA, Small Interfering, Signal Transduction, Transforming Growth Factor beta, Tumor Cells, Cultured, beta Catenin, p38 Mitogen-Activated Protein Kinases
Clin. Exp. Metastasis
Date: Dec. 01, 2014
PubMed ID: 25168821
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