2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.02F.06 Suppression of Chemotherapy Induced Antiviral Signaling by YAP/TAZ in Lung Cancer

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This study explores the role of YAP (Yes-associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif), key effectors in the Hippo signaling pathway, in conferring chemotherapy resistance and suppressing antiviral signaling in non-small cell lung cancer (NSCLC). The study posits that YAP/TAZ activation leads to the expression of genes favoring cell survival, drug efflux, and immune suppression, thereby enabling chemotherapy resistance. Moreover, YAP/TAZ inhibit the antiviral immune response, which naturally enhances chemotherapy efficacy through mechanisms involving interferons (IFNs).<br /><br />The experiments aimed to determine how manipulating YAP/TAZ would influence chemotherapy-induced interferon signaling. The authors designed these experiments to assess the effects of chemotherapy on antiviral signaling in NSCLC and how YAP/TAZ manipulation alters this effect.<br /><br />Key findings reveal that simultaneous knockdown of YAP and TAZ increased the expression of interferon and related genes like CCL5 and CXCL10 in chemotherapy and Poly(I:C) treated lung adenocarcinoma cells. This suggests that restricting YAP/TAZ activity could amplify chemotherapy efficacy, as IFNα2, an interferon type, overlayed with chemotherapy enhanced its effectiveness.<br /><br />Furthermore, YAP/TAZ overexpression provides resistance to interferon-induced cytotoxicity, elucidating their role in immune evasion in cancer cells. The study proposes future research to focus on how YAP/TAZ-mediated suppression of antiviral signaling might affect chemotherapy effectiveness in NSCLC models specifically.<br /><br />The results underscore the therapeutic potential of targeting YAP/TAZ to overcome chemotherapy resistance by reinvigorating antiviral signaling pathways in cancer treatment.

Asset Subtitle

Sharon Khavkine Binstock

Meta Tag

Speaker Sharon Khavkine Binstock

Topic Tumor Biology – Preclinical Biology

Keywords

YAP

TAZ

Hippo signaling pathway

chemotherapy resistance

antiviral signaling

non-small cell lung cancer

interferons

immune suppression

gene expression

cancer treatment