WCLC 2025 - Posters & ePosters-EP.02.02 YB-1 Is a Survival Factor for Mesothelioma-Associated Fibroblasts

Pdf Summary

This study by Pinós et al. investigates the role of Y-box-binding protein 1 (YB-1) in mesothelioma-associated fibroblasts (Meso-CAFs) and its impact on pleural mesothelioma (PM) progression. PM is an aggressive cancer primarily caused by inhalation of asbestos fibers, which resist elimination by macrophages, causing chronic inflammation and activating the tumor microenvironment (TME). This environment induces transformation of pleural cells into pleural mesothelioma cancer cells (PMCs). CAFs, including Meso-CAFs, support tumor growth and dissemination, while YB-1 has been implicated in promoting PM cell growth and migration.<br /><br />The study demonstrates that YB-1 is crucial for Meso-CAF survival and migration. Experimental depletion of YB-1, via specific siRNA knockdown or treatment with the YB-1 inhibitor SU056, significantly reduces YB-1 protein levels, decreases cell viability, proliferation, and migratory capacity of both Meso-CAFs and PMCs. Importantly, while Meso-CAF-conditioned medium does not consistently alter YB-1 expression or phosphorylation in PMCs, knocking down YB-1 in Meso-CAFs impairs their ability to stimulate PMC growth in co-culture experiments.<br /><br />These findings indicate that YB-1 supports Meso-CAF survival and their pro-tumorigenic signaling to PMCs. Although the precise signaling mechanisms require further study, targeting YB-1 in both Meso-CAFs and PMCs could be a promising therapeutic approach to limit PM progression and improve patient outcomes. Given the limited current treatment options for PM, YB-1 inhibition emerges as a potential strategy to enhance the efficacy of existing therapies.

Asset Subtitle

Marc Pinós

Meta Tag

Speaker Marc Pinós

Topic Tumor Biology – Preclinical Biology

Keywords

Y-box-binding protein 1

YB-1

mesothelioma-associated fibroblasts

Meso-CAFs

pleural mesothelioma

PM progression

tumor microenvironment

YB-1 inhibitor SU056

cell viability and migration

therapeutic target