title: EGF-Induced Acetylation of Heterogeneous Nuclear Ribonucleoproteins Is Dependent on KRAS Mutational Status in Colorectal Cancer Cells.
abstract: KRAS mutational status is considered a negative predictive marker of the response to anti-EGFR therapies in colorectal cancer (CRC) patients. However, conflicting data exist regarding the variable response to EGFR-targeted therapy. The effects of oncogenic KRAS on downstream targets were studied in cell lines with different KRAS mutations. Cells harboring a single KRASG13D allele showed the most tumorigenic profile, with constitutive activation of the downstream pathway, rendering them EGF-unresponsive. Conversely, KRASA146T cells showed a full EGF-response in terms of signal transduction pathways, cell proliferation, migration or adhesion. Moreover, the global acetylome of CRC cells was also dependent on KRAS mutational status. Several hnRNP family members were identified within the 36 acetylated-proteins. Acetylation status is known to be involved in the modulation of EGF-response. In agreement with results presented herein, hnRNPA1 and L acetylation was induced in response to EGF in KRASA146T cells, whereas acetyl-hnRNPA1 and L levels remained unchanged after growth factor treatment in KRASG13D unresponsive cells. Our results showed that hnRNPs induced-acetylation is dependent on KRAS mutational status. Nevertheless hnRNPs acetylation might also be the point where different oncogenic pathways converge.
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Desamparados
authors.initials: D
authors.lastname: Roda
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Castillo
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Telechea-Fernández
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: Gil
authors.affiliation: Department of Biochemistry and Molecular Biology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: López-Rodas
authors.affiliation: Department of Biochemistry and Molecular Biology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Luís
authors.initials: L
authors.lastname: Franco
authors.affiliation: Department of Biochemistry and Molecular Biology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: González-Rodríguez
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Roselló
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: J Alejandro
authors.initials: JA
authors.lastname: Pérez-Fidalgo
authors.affiliation: Department of Biochemistry and Molecular Biology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Elena R
authors.initials: ER
authors.lastname: García-Trevijano
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Cervantes
authors.affiliation: Department of Haematology and Medical Oncology, INCLIVA Biomedical Research Institute / University of Valencia, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Zaragozá
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; C117307:KRAS protein, human; D004815:Epidermal Growth Factor; D016283:Proto-Oncogene Proteins p21(ras)