TGFβ can stimulate the p38/β-catenin/PPARγ signaling pathway to promote the EMT, invasion and migration of non-small cell lung cancer (H460 cells)

Abstract

Signaling pathway(s) responsible for transforming growth factor β (TGFβ)-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 TGFβ-induced p(38)/β-catenin/PPARγ signaling pathway played a critical role in the promotion of EMT, invasion and migration of H460 cells. All these pathological outcomes attributed to PPARγ-increased expression of p-EGFR, p-c-MET and Vimentin and the decrease of E-cadherin. Transforming growth factor β and p(38)-induced β-catenin not only stimulated the expression of PPARγ but also physically interacted with it. Blocking the ligand binding domain of PPARγ (with GW9662) could significantly interfere the binding between PPARγ and β-catenin, and interrupt the nuclear infiltration of both factors. These findings suggested that β-catenin was an upstream regulator and a ligand of PPARγ, and the binding between these two molecules was critical for their nuclear infiltration. Transforming growth factor β-induced tumor invasion and migration was also seen in U373 cells (brain glioma, with high inducible PPARγ) in a PPARγ-dependent manner, but not in CH27 cells (squamous NSCLC, with low PPARγ). PPARγ shRNA, GW9662, JW67 and 2,4-diaminoquinazoline were all revealed to have important values in the control of the intrinsic and TGFβ-induced EMT, tumor invasion and migration of H460 cells. The results further suggested that PPARγ and β-catenin may be the potential markers for the early diagnosis and/or treatment of metastatic tumors.

Tumor Budding, Micropapillary Pattern, and Polyploidy Giant Cancer Cells in Colorectal Cancer: Current Status and Future Prospects

“…Tumor budding was characterized by increased expression for both β -catenin and p16 (cyclin-dependent kinase inhibitor 2A) [68]. β -Catenin is important for linkage of E-cadherins to the cytoskeleton [80, 81]. The downregulation of E-cadherin in carcinoma cells is associated with increased invasive ability of cancer cells [82, 83].…”

Long noncoding RNA BX357664 regulates cell proliferation and epithelial-to-mesenchymal transition via inhibition of TGF-β1/p38/HSP27 signaling in renal cell carcinoma

“…Recent studies have identified several signaling pathways for TGF-β-induced EMT [22]. In particular, the TGF-β/p38 mitogen-activated protein kinase (MAPK) signaling pathway is a well-investigated inducer of EMT in a variety of cancers, including lung cancer, renal cancer, breast cancer, and liver cancer [26-29]. …”

Transforming growth factor-β, MAPK and Wnt signaling interactions in colorectal cancer

“…It is important to note that another study reported that TGFb suppresses b-catenin/Wnt signaling and enhances cell adhesion in CRC in a Smad4-independent manner [132]. A similar study to that of Demangy et al, reported the ability of TGFb to promote the EMT and invasion in a p38 MAPK/b-catenin/peroxisome proliferator-activated receptor g-dependent manner in non-small cell lung cancers [137].…”