Fig. 4: Transcriptomics of FA deficient patient samples demonstrate similar hallmarks of lysosomal and lysosomal exocytosis dysregulation.

a Publicly available patient transcriptomic data that analyzed differential expressed genes from FA SCC patient tumors in comparison to sporadic HNSCC [58] confirmed a lysosomal/lysosomal exocytosis phenotype. All down regulated genes that had a statistically significant gene expression difference (p-value < 0.005) by at least a 1.5-fold were used as input for GO analysis (ShinyGO v0.77) [7]. The results show enrichment in lysosome related functions that are highlighted with red asterisks. b TFEB levels were measured using qPCR in FaDu, Cal33, and UM-SCC-01 FA-null mutants (n = 3 biological replicates each with n = 4 technical PCR replicates; Mean ± STD, unpaired two-tailed t-test was used to determine statistical significance). c A model of how deficiencies in FA pathway can lead to lysosomal defects and reliance on lysosomal exocytosis. The genomic stress that the loss of specific FA proteins causes replicative stress, DNA damage, and increase in oxidative stress. To combat these effects, there is dysregulation of autophagy and lysosomal biogenesis/health. This compromised state allows the cell to survive the loss of the FA pathway but renders the cell in a suboptimal state the is reliant on lysosomal exocytosis.