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Supplementary Figures 1-9 from VEGF Exerts an Angiogenesis-Independent Function in Cancer Cells to Promote Their Malignant Progression

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posted on 2023-03-30, 21:15 authored by Ying Cao, Guangqi E, Enfeng Wang, Krishnendu Pal, Shamit K. Dutta, Dafna Bar-Sagi, Debabrata Mukhopadhyay

PDF file - 824K, 1) Supplementary Figure S1. VEGF knock down in RCC cells restricted the tumor size and induced a differentiation phenotype in vivo. 2) Supplementary Figure S2. VEGF knock down in RCC cells restricted the tumor phenotypes in vitro. 3) Supplementary Figure S3. VEGF knockdown did not affect 786-O and A-498 cell proliferation and apoptosis. 4) Supplementary Figure S4. Induction of VEGF shRNA ((+)Dox) reduced A-498 cells anchorage independent clonogenic ability. 5) Supplementary Figure S5. Low concentration (0.2ug/ml) Doxycycline did not have a significant effect on A-498 cell proliferation, apoptosis, differentiation, or tumor formation. 6) Supplementary Figure S6. Mouse xenograft model of VEGF in tumorigenesis using a GFP/RFP combination system. 7) Supplementary Figure S7. The distribution of GFP and RFP labeled cells and the vascular densities in the tumor tissue. 8) Supplementary Figure S8. ERK1/2 and AKT were activated by VEGF. 9) Supplementary Figure S9. Knockdown of SOS1/2 induced 786-O cells into a differentiation phenotype.

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ARTICLE ABSTRACT

VEGF/vascular permeability factor (VEGF/VPF or VEGF-A) is a pivotal driver of cancer angiogenesis that is a central therapeutic target in the treatment of malignancy. However, little work has been devoted to investigating functions of VEGF that are independent of its proangiogenic activity. Here, we report that VEGF produced by tumor cells acts in an autocrine manner to promote cell growth through interaction with the VEGF receptor neuropilin-1 (NRP-1). Reducing VEGF expression by tumor cells induced a differentiated phenotype in vitro and inhibited tumor forming capacity in vivo, independent of effects on angiogenesis. Autocrine activation of tumor cell growth was dependent on signaling through NRP-1, and Ras was determined to be a critical effector signaling molecule downstream of NRP-1. Our findings define a novel function for VEGF in dedifferentiation of tumor cells expanding its role in cancer beyond its known proangiogenic function. Cancer Res; 72(16); 3912–8. ©2012 AACR.

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