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1. Supplemental Figure 5 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Figure S5. VEGF-D 5'UTR mRNA exhibits two structural forms that allow the binding of different proteins

Published
2023
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2. Supplemental Figure 2 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Figure S2. Expression of endogenous VEGF-D in mice tissues

Published
2023
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3. Supplemental Figure 7 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Figure S7. Tumor growth after NSAID treatment

Published
2023
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4. Data from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

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.

Published
2023
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5. Supplemental Figure 8 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Figure S8. Schematic representation of VEGF-D synthesis in tumor cells

Published
2023
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6. Supplementary Figure Legend from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Supplementary figure legend

Published
2023
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7. Supplemental Figure 6 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Figure S6. Polysome profiling of 4T1 cells

Published
2023
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8. Supplemental Figure 4 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Figure S4. Lymphangiogenesis and tumor gowth are not affected by 4T1 or 67NR lentiviral transduction

Published
2023
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9. Supplemental Figure 3 from Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Barbara H. Garmy-Susini, Anne-Catherine Prats, Robert J. Schneider, Stefano Marzi, Julie Guillermet-Guibert, Jose Courty, Stephane Pyronnet, Frederic Lopez, Laetitia Ligat, Anne Gomez-Brouchet, Françoise Pujol, Stephanie Cassant-Sourdy, Anne-Catherine Helfer, Aurelien Adoue, Fransky Hantelys, Florence Tatin, and Florent Morfoisse

Abstract

Figure S3. Podoplanin staining of lymphatic vessels

Published
2023
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10. Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Author

Stefano Marzi, Stéphanie Cassant-Sourdy, José Courty, Aurelien Adoue, Anne-Catherine Prats, Frédéric Lopez, Anne-Catherine Helfer, Julie Guillermet-Guibert, Barbara Garmy-Susini, Anne Gomez-Brouchet, Robert J. Schneider, Françoise Pujol, Fransky Hantelys, Laetitia Ligat, Stéphane Pyronnet, Florent Morfoisse, Florence Tatin, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Vascular Endothelial Growth Factor D, Biology, Transfection, Mice, 03 medical and health sciences, chemistry.chemical_compound, Protein biosynthesis, Animals, Humans, Gene silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Lymphangiogenesis, ComputingMilieux_MISCELLANEOUS, Messenger RNA, fungi, RNA-Binding Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Translation (biology), Phosphoproteins, Molecular biology, 3. Good health, Cell biology, Vascular endothelial growth factor, Internal ribosome entry site, 030104 developmental biology, Oncology, chemistry, Nucleolin
Abstract

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.

Published
2016
Full Text
View/download PDF

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