Fig. 3: Cetuximab resistance is associated with increased fatty acid uptake and oxidation in HNSCC cells. | Nature Communications

Fig. 3: Cetuximab resistance is associated with increased fatty acid uptake and oxidation in HNSCC cells.

From: PPARα-mediated lipid metabolism reprogramming supports anti-EGFR therapy resistance in head and neck squamous cell carcinoma

Fig. 3

Oxygen consumption rate (OCR) of cetuximab-sensitive (-S) and -resistant (-R) FaDu (a) and SC263 cells (b) in media containing either glucose (Glc), glutamine (Gln), or palmitate (PA) (N = 3, n = 6). c Quantification for BODIPY FL C16 uptake in cetuximab-sensitive (-S) and -resistant (-R) FaDu and SC263 cells (N = 3). d Intracellular abundance of FAcyl-CoA (i.e. palmitoyl-CoA, palmitoleyl-CoA, oleyl-CoA, stearoyl-CoA) in cetuximab-sensitive (-S) and -resistant (-R) FaDu and SC263 cells (N = 3). mRNA expression (e) and representative immunoblotting (f) for CD36 in cetuximab-sensitive (-S) and -resistant (-R) FaDu and SC263 cells (N = 3). g Quantification for BODIPY FL C16 uptake in cetuximab-sensitive (-S) and -resistant (-R) FaDu cells upon transfection of siRNA against CD36 gene for 72 h (N = 2). mRNA expression (h) and representative immunoblotting (i) for CPT1A in cetuximab-sensitive (-S) and -resistant (-R) FaDu and SC263 cells (N = 3, n = 3). j Palmitate-dependent OCR in cetuximab-sensitive (-s) and -resistant (-R) FaDu cells upon treatment with 100 µM etomoxir for 30 min (N = 3, n = 6). k Intracellular abundance of acetyl-CoA in cetuximab-sensitive (-S) and -resistant (-R) FaDu cells upon treatment with 100 µM etomoxir for 3 h (N = 3). l Heatmap showing the upstream regulators (X-axis) of ACACA, CPT1A and FASN (Y-axis) in the protein-protein interaction network identified in Fig. 1. Upstream regulators directly interact with any of the proteins of interest (i.e. network distance of 1) and are differentially expressed or activated between cetuximab-resistant and -sensitive HNSCC cells. The direction and level of differential activation and/or repression is color-coded as shown in the legend underneath the heatmap. Data are plotted as the means ± SEM. N indicates the number of independent biological experiments and n indicates the number of technical replicates (when >1). Significance was determined by two-way ANOVA with Sidák’s multiple comparison test (a–e, h and j, k). P-values as indicated or ***P < 0.001; ns not significant. Source data are provided as a Source Data file.

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