Secreted Pyruvate Kinase M2 Promotes Lung Cancer Metastasis through Activating the Integrin Beta1/FAK Signaling Pathway

Abstract

Summary: Cancer cell-derived secretomes have been documented to play critical roles in cancer progression. Intriguingly, alternative extracellular roles of intracellular proteins are involved in various steps of tumor progression, which can offer strategies to fight cancer. Herein, we identify lung cancer progression-associated secretome signatures using mass spectrometry analysis. Among them, PKM2 is verified to be highly expressed and secreted in lung cancer cells and clinical samples. Functional analyses demonstrates that secreted PKM2 facilitates tumor metastasis. Furthermore, mass spectrometry analysis and functional validation identify integrin β1 as a receptor of secreted PKM2. Mechanistically, secreted PKM2 directly bound to integrin β1 and subsequently activated the FAK/SRC/ERK axis to promote tumor metastasis. Collectively, our findings suggest that PKM2 is a potential serum biomarker for diagnosing lung cancer and that targeting the secreted PKM2-integrin β1 axis can inhibit lung cancer development, which provides evidence of a potential therapeutic strategy in lung cancer. : Wang et al. find that PKM2 is highly expressed and secreted in lung cancer. Secreted PKM2 facilitates metastasis by interacting with its receptor integrin β1, which activates the FAK/SRC/ERK pathway and subsequently elevates MMP-9 expression. These results suggest that secreted PKM2 and integrin β1 are potential targets in lung cancer patients. Keywords: integrin β1, lung cancer, metastasis, PKM2, secretome