title: Myc requires RhoA/SRF to reprogram glutamine metabolism.
abstract: RhoA regulates actin cytoskeleton but recent evidence suggest a role for this conserved Rho GTPase also in other cellular processes, including transcriptional control of cell proliferation and survival. Interestingy, loss of RhoA is synthetic lethal with oncogenic Myc, a master transcription factor that turns on anabolic metabolism to promote cell growth in many cancers. We show evidence indicating that the synthetic lethal interaction between RhoA loss and Myc arises from deficiency in glutamine utilization, resulting from impaired co-regulation of glutaminase expression and anaplerosis by Myc and RhoA - serum response factor (SRF) pathway. The results suggest metabolic coordination between Myc and RhoA/SRF in sustaining cancer cell viability and indicate RhoA/SRF as a potential vulnerability in cancer cells for therapeutic targeting.
authors.affiliation: a Cancer Cell Circuitry Laboratory, Research Programs Unit/Translational Cancer Biology & Institute of Biomedicine, University of Helsinki , Helsinki , Finland.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Haikala
authors.affiliation: a Cancer Cell Circuitry Laboratory, Research Programs Unit/Translational Cancer Biology & Institute of Biomedicine, University of Helsinki , Helsinki , Finland.
authors.forename: Elsa
authors.initials: E
authors.lastname: Marques
authors.affiliation: b Research Programs Unit/Genome-Scale Biology and Department of Pathology , Haartman Institute, University of Helsinki , Helsinki , Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Turunen
authors.affiliation: a Cancer Cell Circuitry Laboratory, Research Programs Unit/Translational Cancer Biology & Institute of Biomedicine, University of Helsinki , Helsinki , Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Klefström
mesh_terms: D045744:Cell Line, Tumor; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D026362:Serum Response Factor / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D026362:Serum Response Factor; D005973:Glutamine; D020742:rhoA GTP-Binding Protein
keywords: Myc; RhoA; SRF; apoptosis; breast cancer; glutamine metabolism