Super-ResolutionFluorescence Imaging Reveals theMechanism of NRP1 Clustering on Non-Small-Cell Lung Cancer Membranes

Neuropilin 1 (NRP1) is upregulated in various types of malignant tumors, especially non-small-cell lung cancer (NSCLC). However, the precise mechanisms for membrane localization and regulation are not fully understood. Observations from super-resolution microscopy have revealed that NRP1 tends to form nanoscale clusters on the cell membrane, with these clusters varying significantly in size and density across different regions. Further research has shown that stimulation by hepatocyte growth factor (HGF) can reorganize the distribution of NRP1, reducing the number of small clusters while promoting the formation of larger ones. This suggests a propensity for internalization after activation. Additionally, dual-color dSTORM imaging has demonstrated a certain degree of colocalization between NRP1 and c-MET, indicating that c-MET plays an important role in stabilizing NRP1 clusters. This study provides new insights into the mechanism behind NRP1’s clustered distribution on cell membranes and paves the way for developing more effective therapeutic strategies targeting NRP1 within tumors.