2023 World Conference on Lung Cancer (Posters)-EP06.06. Fibronectin Promotes Tumor Angiogenesis and Progression of Non-small-Cell Lung Cancer

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A study conducted by researchers at the Shanghai Pulmonary Hospital in China has found that fibronectin, an extracellular matrix protein, plays a crucial role in promoting angiogenesis and progression of non-small-cell lung cancer (NSCLC). Previous studies have indicated that fibronectin is associated with cancer stemness, angiogenesis, and progression in various cancer types, but its involvement in NSCLC had not been fully understood until now.<br /><br />The researchers used a public dataset to determine the prognostic significance of genes and conducted immunohistochemistry, WB, RNA-seq, and rescue experiments. They found that fibronectin was up-regulated in NSCLC tissues compared to normal tissues. Furthermore, fibronectin promoted tumor growth, metastasis, and angiogenesis of NSCLC in both in vitro and in vivo models by enhancing epithelial-mesenchymal transition (EMT) and maintaining stemness of NSCLC cells.<br /><br />They discovered that fibronectin activates FAK and its downstream MAPK/ERK signaling pathway. Additionally, they identified WISP3 as a potential target gene of fibronectin. Activation of WISP3 effectively activated the Wnt signaling pathway, whereas knockdown of WISP3 blocked the influence of fibronectin on migration, invasion, and vascular structure formation potential of NSCLC cells.<br /><br />The researchers also found that fibronectin elevated the transcription of the WISP3 gene by promoting the binding of HIF-1α to the promoter region of WISP3 in NSCLC cells. The study provides insights into the mechanism by which fibronectin promotes the progression of NSCLC.<br /><br />In conclusion, the study outlines the route through which fibronectin exerts its role in NSCLC. Fibronectin activates FAK and MAPK/ERK signaling pathways, leading to the accumulation of HIF-1α. HIF-1α then enables the transcription of WISP3, which promotes the activation of the Wnt signaling pathway and subsequently enhances tumor growth, metastasis, and angiogenesis in NSCLC. This study sheds light on the potential of fibronectin as a therapeutic target for NSCLC treatment.

Asset Subtitle

Guanghui Gao

Meta Tag

Speaker Guanghui Gao

Topic Pathology & Biomarkers: Prognostic Biomarkers

Keywords

fibronectin

extracellular matrix protein

angiogenesis

non-small-cell lung cancer

NSCLC

cancer stemness

epithelial-mesenchymal transition

FAK

MAPK/ERK signaling pathway

WISP3