American Association for Cancer Research
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Supplemental Figure 6 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

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posted on 2023-03-31, 00:06 authored by Florent Morfoisse, Florence Tatin, Fransky Hantelys, Aurelien Adoue, Anne-Catherine Helfer, Stephanie Cassant-Sourdy, Françoise Pujol, Anne Gomez-Brouchet, Laetitia Ligat, Frederic Lopez, Stephane Pyronnet, Jose Courty, Julie Guillermet-Guibert, Stefano Marzi, Robert J. Schneider, Anne-Catherine Prats, Barbara H. Garmy-Susini

Figure S6. Polysome profiling of 4T1 cells


Ligue Régionale Contre le Cancer

Association pour la Recherche sur le Cancer

the foundation Lefoulon Delalande

IDEX Paul Sabatier Federal University



The vascular endothelial growth factor VEGF-D promotes metastasis by inducing lymphangiogenesis and dilatation of the lymphatic vasculature, facilitating tumor cell extravasion. Here we report a novel level of control for VEGF-D expression at the level of protein translation. In human tumor cells, VEGF-D colocalized with eIF4GI and 4E-BP1, which can program increased initiation at IRES motifs on mRNA by the translational initiation complex. In murine tumors, the steady-state level of VEGF-D protein was increased despite the overexpression and dephosphorylation of 4E-BP1, which downregulates protein synthesis, suggesting the presence of an internal ribosome entry site (IRES) in the 5′ UTR of VEGF-D mRNA. We found that nucleolin, a nucleolar protein involved in ribosomal maturation, bound directly to the 5′UTR of VEGF-D mRNA, thereby improving its translation following heat shock stress via IRES activation. Nucleolin blockade by RNAi-mediated silencing or pharmacologic inhibition reduced VEGF-D translation along with a subsequent constriction of lymphatic vessels in tumors. Our results identify nucleolin as a key regulator of VEGF-D expression, deepening understanding of lymphangiogenesis control during tumor formation. Cancer Res; 76(15); 4394–405. ©2016 AACR.

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