Fig. 8 | Signal Transduction and Targeted Therapy

Fig. 8

From: SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer

Fig. 8

Blocking the transmission of EV-packaged circTLCD4-RWDD3 suppresses LN metastasis of NSCLC. a, b Representative bioluminescence images (a) and quantification (b) of popliteal metastatic LNs from nude mice treated with EVs secreted by control or circTLCD4-RWDD3-overexpressing A549 cells with or without mutating SIM in ALIX (n = 12 per group). (c) Quantification of popliteal LN volume of nude mice treated with EVs (n = 12 per group). d Kaplan–Meier curves show the survival of nude mice treated with EVs secreted by control or circTLCD4-RWDD3-overexpressing A549 cells with or without mutating SIM in ALIX. e–g Representative IHC images and percentages of PROX1- or LYVE-1-indicated lymphatic vessel density in footpad primary tumor tissues. Scale bars, 50 µm. h Representative fluorescence images to confirm the correlation for circTLCD4-RWDD3 expression, UBC9 and PROX1 expression, and LYVE-1-indicated MLD in the serial section of NSCLC tissues from the multicenter cohorts (n = 312). Scale bars, 50 μm. The statistical difference was assessed through one-way ANOVA followed by Dunnett tests in (b, c, f, and g). Error bars show the SD from three independent experiments. *P < 0.05; **P < 0.01

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