The eukaryotic translation initiation factor eIF4E harnesses hyaluronan production to drive its malignant activity.

Autor: Zahreddine HA; Department of Pathology and Cell Biology, Institute for Research in Immunology and Cancer, Université de Montréal, Québec, Canada., Culjkovic-Kraljacic B; Department of Pathology and Cell Biology, Institute for Research in Immunology and Cancer, Université de Montréal, Québec, Canada., Emond A; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Québec, Canada., Pettersson F; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Québec, Canada., Midura R; Orthopaedic Research Center, The Cleveland Clinic Foundation, Cleveland, United States.; Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, United States., Lauer M; Orthopaedic Research Center, The Cleveland Clinic Foundation, Cleveland, United States.; Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, United States., Del Rincon S; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Québec, Canada., Cali V; Orthopaedic Research Center, The Cleveland Clinic Foundation, Cleveland, United States.; Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, United States., Assouline S; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Québec, Canada., Miller WH; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Québec, Canada., Hascall V; Orthopaedic Research Center, The Cleveland Clinic Foundation, Cleveland, United States.; Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, United States., Borden KL; Department of Pathology and Cell Biology, Institute for Research in Immunology and Cancer, Université de Montréal, Québec, Canada.
Jazyk: angličtina
Zdroj: ELife [Elife] 2017 Nov 07; Vol. 6. Date of Electronic Publication: 2017 Nov 07.
DOI: 10.7554/eLife.29830
Abstrakt: The microenvironment provides a functional substratum supporting tumour growth. Hyaluronan (HA) is a major component of this structure. While the role of HA in malignancy is well-defined, the mechanisms driving its biosynthesis in cancer are poorly understood. We show that the eukaryotic translation initiation factor eIF4E, an oncoprotein, drives HA biosynthesis. eIF4E stimulates production of enzymes that synthesize the building blocks of HA, UDP-Glucuronic acid and UDP-N-Acetyl-Glucosamine, as well as hyaluronic acid synthase which forms the disaccharide chain. Strikingly, eIF4E inhibition alone repressed HA levels as effectively as directly targeting HA with hyaluronidase. Unusually, HA was retained on the surface of high-eIF4E cells, rather than being extruded into the extracellular space. Surface-associated HA was required for eIF4E's oncogenic activities suggesting that eIF4E potentiates an oncogenic HA program. These studies provide unique insights into the mechanisms driving HA production and demonstrate that an oncoprotein can co-opt HA biosynthesis to drive malignancy.
Databáze: MEDLINE
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