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http://purl.uniprot.org/citations/32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32434218http://www.w3.org/2000/01/rdf-schema#comment"Despite a critical role for MYC as an effector of oncogenic RAS, strategies to target MYC activity in RAS-driven cancers are lacking. In genetically engineered mouse models of lung and pancreatic cancer, oncogenic KRAS is insufficient to drive tumorigenesis, while addition of modest MYC overexpression drives robust tumor formation, suggesting that mechanisms beyond the RAS pathway play key roles in MYC regulation and RAS-driven tumorigenesis. Here we show that acidic fibroblast growth factor (FGF1) derived from cancer-associated fibroblasts (CAFs) cooperates with cancer cell-autonomous signals to increase MYC level, promoter occupancy, and activity. FGF1 is necessary and sufficient for paracrine regulation of MYC protein stability, signaling through AKT and GSK-3β to increase MYC half-life. Patient specimens reveal a strong correlation between stromal CAF content and MYC protein level in the neoplastic compartment, and identify CAFs as the specific source of FGF1 in the tumor microenvironment. Together, our findings demonstrate that MYC is coordinately regulated by cell-autonomous and microenvironmental signals, and establish CAF-derived FGF1 as a novel paracrine regulator of oncogenic transcription."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.org/dc/terms/identifier"doi:10.1084/jem.20191805"xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/author"Bhattacharyya S."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/author"Link J."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/author"Sears R.C."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/author"Sherman M.H."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/author"Kothari A."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/author"Horton W."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/author"Oon C."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/name"J Exp Med"xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/pages"e20191805"xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/title"Acidic fibroblast growth factor underlies microenvironmental regulation of MYC in pancreatic cancer."xsd:string
http://purl.uniprot.org/citations/32434218http://purl.uniprot.org/core/volume"217"xsd:string
http://purl.uniprot.org/citations/32434218http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32434218
http://purl.uniprot.org/citations/32434218http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32434218
http://purl.uniprot.org/uniprot/#_A0A0B4J1R1-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218
http://purl.uniprot.org/uniprot/#_A8K147-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218
http://purl.uniprot.org/uniprot/#_A0N2G3-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218
http://purl.uniprot.org/uniprot/#_A0A224B085-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218
http://purl.uniprot.org/uniprot/#_B3CJ86-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218
http://purl.uniprot.org/uniprot/#_B3CJ87-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218
http://purl.uniprot.org/uniprot/#_B3CJ88-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218
http://purl.uniprot.org/uniprot/#_B3CJB2-mappedCitation-32434218http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32434218