Fig. 3: Low BMI-mediated neuronal NPY promotes brain metastasis via Y5R signaling.
From: Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI
A Violin and dot plots analysis showing NPY receptor expression in matched brain metastatic samples from lung, breast, and melanoma cancer patients using GEO datasets (GSE200563 - upper; GSE125989 and GSE44660 -lower panels; unpaired two-tailed t-test). B qRT-PCR analysis of Y5R expression in brain metastatic tissue from lung cancer patients with low and high BMI (n = 7/group), normalized to β-Actin (unpaired two-tailed t-test). C qRT-PCR analysis of Y5R expression in human and mouse lung cancer cell lines treated with 100 nM rNPY, normalized to β-Actin (n = 3 independent experiments, unpaired two-tailed t-test). D Gene Set Enrichment Analysis (GSEA) of neuropeptide receptor activity in matched lung (n = 30) and brain metastatic tumors (n = 27) from GSE200563, using pre-ranked MSigDB v5.1gene sets. Enrichment scores generated by random forest-based ranking; p-values indicate statistical significance. E Bar plot showing enriched signaling pathways in Y5Rhigh and Y5Rlow lung cancer brain metastasis (GSE200563). F Pearson correlation between Y5R and MAPK family members in brain metastatic patients (n = 27, GSE200563; two-tailed); Y5R-ERK5 (p = 0.0003), Y5R-JNK (p = 0.04) and Y5R-p38 (p = 0.853). G Left: Schematic of in vivo metastasis assay. Female C57BL/6 mice (5–6 weeks) were fed with a standard or 50% CRD (12-hr/dark phase) for 15 days before ScrKO and y5rKO CMT167 cells injection (5 × 104; i.c.). Right: Average body weight curve (two-way ANOVA with Tukey’s test). H Representative in vivo (top) and ex vivo (bottom) BLI images of brain metastasis at endpoint. I Top: In vivo (n = 9/group; left) and ex vivo (n = 7/group; right) BLI quantification of brain metastasis in ScrKO and y5rKO implanted mice [two-way ANOVA with Tukey’s test (in vivo); unpaired two-tailed t-test (ex vivo)]. Bottom: Kaplan–Meier analysis of brain metastasis-free survival in ScrKO and y5rKO implanted mice [n = 9/group; log-rank (Mantel–Cox test)]. J Representative ex vivo BLI images and quantification of extracranial metastasis in ScrKO and y5rKO implanted mice (n = 7/group) at endpoint (unpaired two-tailed t-test). All data are mean ± S.E.M. Source data are provided as a Source Data file.
