hnRNP A1-mediated translational regulation of the G quadruplex-containing RON receptor tyrosine kinase mRNA linked to tumor progression

• DOI: 10.18632/oncotarget.7589
• Publication Date: 2016-02-22T21:07:37Z
• Authors: Anne Cammas; Magali Lacroix-Triki; Sandra Pierredon; Morgane Le Bras; Jason S. Iacovoni; Marie-Paule Teula...; Gilles Favre; Henri Roché; Thomas Filleron; Stefania Millevoi; Stéphan Vagner
• Keywords: 0301 basic medicine; 570; [SDV]Life Sciences [q-bio]; Heterogeneous Nuclear Ribonucleoprotein A1; 610; Receptor Protein-Tyrosine Kinases; Breast Neoplasms; Kaplan-Meier Estimate; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Protein Biosynthesis; Disease Progression; Humans; Female; RNA, Messenger; Research Paper

The expression and role of RNA binding proteins (RBPs) controlling mRNA translation during tumor progression remains largely uncharacterized. Analysis by immunohistochemistry of the expression of hnRNP A1, hnRNPH, RBM9/FOX2, SRSF1/ASF/SF2, SRSF2/SC35, SRSF3/SRp20, SRSF7/9G8 in breast tumors shows that the expression of hnRNP A1, but not the other tested RBPs, is associated with metastatic relapse. Strikingly, hnRNP A1, a nuclear splicing regulator, is also present in the cytoplasm of tumor cells of a subset of patients displaying exceedingly worse prognosis. Expression of a cytoplasmic mutant of hnRNP A1 leads to increased translation of the mRNA encoding the tyrosine kinase receptor RON/MTS1R, known for its function in tumor dissemination, and increases cell migration in vitro. hnRNP A1 directly binds to the 5' untranslated region of the RON mRNA and activates its translation through G-quadruplex RNA secondary structures. The correlation between hnRNP A1 and RON tumoral expression suggests that these findings hold clinical relevance.