Tumor Microenvironmental Cytokines Drive NSCLC Cell Aggressiveness and Drug-Resistance via YAP-Mediated Autophagy

Abstract

Dynamic reciprocity between cellular components of the tumor microenvironment and tumor cells occurs primarily through the interaction of soluble signals, i.e., cytokines produced by stromal cells to support cancer initiation and progression by regulating cell survival, differentiation and immune cell functionality, as well as cell migration and death. In the present study, we focused on the analysis of the functional response of non-small cell lung cancer cell lines elicited by the treatment with some crucial stromal factors which, at least in part, mimic the stimulus exerted in vivo on tumor cells by microenvironmental components. Our molecular and functional results highlight the role played by the autophagic machinery in the cellular response in terms of the invasive capacity, stemness and drug resistance of two non-small lung cancer cell lines treated with stromal cytokines, also highlighting the emerging role of the YAP pathway in the mutual and dynamic crosstalk between tumor cells and tumor microenvironment elements. The results of this study provide new insights into the YAP-mediated autophagic mechanism elicited by microenvironmental cytokines on non-small cell lung cancer cell lines and may suggest new potential strategies for future cancer therapeutic interventions.

Keywords

• non-small cell lung cancer (NSCLC)
• autophagy
• cytokines
• microenvironment
• cancer progression
• epithelial-mesenchymal transition (EMT)