Super-resolution imaging reveals the role of DDR1 cluster in NSCLC proliferation.

Discoidin domain receptor 1 (DDR1), a transmembrane protein, is crucial in tumor development. Prior studies have demonstrated a significant correlation between protein cluster distribution on the cell membrane and tumor evolution. However, the precise spatial distribution characteristics of DDR1 on cell membranes and their impact on tumor development remain unclear. In this study, we conducted gene expression analysis to investigate DDR1 expression in non-small cell lung cancer (NSCLC) and its association with patient prognosis. We also employed direct stochastic optical reconstruction microscopy (dSTORM) imaging to examine DDR1's spatial distribution in NSCLC cells and tissues. Our findings indicate that DDR1 forms larger, tighter, and more abundant clusters in cancer cells and tissues compared to their normal counterparts. Notably, we observed that the enhanced aggregation of DDR1 clusters increased the likelihood of interaction with SRC, thereby activating the SRC-STAT3 signaling pathway in NSCLC cells and promoting cell proliferation. This study provides novel insights into the role of DDR1 aggregation in tumor proliferation, confirms DDR1 as a potential tumor marker, and serves as a valuable resource for future drug development.