Title: Microenvironmental cues co-regulate pancreatic cancer metabolism and histone acetylation

Accession Number: GSE70971

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70971

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Genome binding/occupancy profiling by high throughput sequencing

Organism(s): Homo sapiens

Summary: To investigate the paracrine effects of stromal elements on cancer cells, we developed a “stromal” culture system, which incorporates structural and diffusible stroma-derived elements into homotypic cultures amenable to functional genomics and metabolomics. We show that microenvironmental cues co-regulate cancer metabolism and gene expression. Stromal inputs broadly influence histone acetylation in the cancer epigenome, coinciding with induction of genes implicated in anabolic metabolism and inflammation. The gene expression and metabolic changes induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and microenvironmental pathways. We implicate the BET family of epigenetic readers as key transducers of stromal inputs to drive alterations in gene expression and suggest paracrine epigenome regulation as a conduit through which stromal signals drive metabolic and immune adaptation to a challenging tumor microenvironment.

Publication(s) associated with this dataset:

• Sherman MH, Yu RT, Tseng TW, Sousa CM, Liu S, Truitt ML, He N, Ding N, Liddle C, Atkins AR, Leblanc M, Collisson EA, Asara JM, Kimmelman AC, Downes M, Evans RM. 2017. Stromal cues regulate the pancreatic cancer epigenome and metabolome. Proc Natl Acad Sci U S A 114(5):1129-1134. doi:10.1073/pnas.1620164114 PMID:28096419 PMCID:PMC5293019