Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4/?-catenin/PPAR? signalling.

ABSTRACT: Cancer-associated fibroblasts (CAFs) contribute to tumour epithelial-mesenchymal transition (EMT) via interaction with cancer cells. However, the molecular mechanisms underlying tumour-promoting EMT of CAFs in lung adenocarcinoma (ADC) remain unclear. Here, we observed that CAFs isolated from lung ADC promoted EMT via production of stromal cell-derived factor-1 (SDF-1) in conditioned medium (CM). CAF-derived SDF-1 enhanced invasiveness and EMT by upregulating CXCR4, ?-catenin, and PPAR?, while downregulating these proteins reversed the effect. Furthermore, RNAi-mediated CXCR4 knockdown suppressed ?-catenin and PPAR? expression, while ?-catenin inhibition effectively downregulated PPAR? without affecting CXCR4; however, treatment with a PPAR? inhibitor did not inhibit CXCR4 or ?-catenin expression. Additionally, pairwise analysis revealed that high expression of CXCR4, ?-catenin, and PPAR? correlated positively with 75 human lung adenocarcinoma tissues, which was predictive of poor prognosis. Thus, targeting the CAF-derived, SDF-1-mediated CXCR4 ?-catenin/ PPAR? cascade may serve as an effective targeted approach for lung cancer treatment.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC7910618 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature