Phosphoethanolamine Accumulation Protects Cancer Cells under Glutamine Starvation through Downregulation of PCYT2

The conditions of the tumor microenvironment, such as nutrient starvation, play critical roles in cancer progression. However, the role of glutamine deprivation in cancer progression is not studied as extensively as that of hypoxia. Here, we show that glutamine starvation triggered down-regulation of PCYT2 by stimulating accumulation of PEtn. Interestingly, glutamine upregulated series of glutamine-responsive genes, not only PCYT2. Furthermore, glutamine-responsive genes were associated with overall survival of cancer patients. Thus, our findings show that glutamine responsive genes such as PCYT2 are key for progression of cancer cells, partly protecting cancer cells to glutamine starvation. Overall design: Cells were treated for 24 h under each condition. RNA-seq reads were aligned to human transcriptome (UCSC gene) and genome (GRCh37/hg19) references respectively using Burrows-Wheeler Aligner. After transcript coordinate was converted to genomic positions, an optimal mapping result was selected either from transcript or genome mapping by comparing the minimal edit distance to the reference. Local realignment was performed within in-house short reads aligner with smaller k-mer size (k=11). Finally, fragments per kilobase of exon per million fragment mapped (FPKM) values were calculated for each UCSC gene while considering strand-specific information.