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Intracrine vascular endothelial growth factor signaling in survival and chemoresistance of human colorectal cancer cells

Oncogene volume 30, pages 1205–1212 (2011)Cite this article

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Abstract

Although the effects of vascular endothelial growth factor (VEGF) on angiogenesis and vascular function are well known, the effects of VEGF on tumor cell function remain to be elucidated. We studied phenotypic changes in human colorectal cancer (CRC) cells with homozygous deletion of VEGF alleles to determine the potential direct role of VEGF on tumor cell function. Loss of VEGF expression led to significantly decreased cell growth and increased spontaneous apoptosis in CRC cells (P<0.01). Loss of VEGF also increased the in vitro sensitivity of cells to the cytotoxic effects of the chemotherapeutic drug 5-fluorouracil, as shown by increased apoptosis (P<0.05). These effects were mediated via upregulation of the proapoptotic mediators caspase-3, cleaved PARP and Bax and downregulation of the pro-survival mediator survivin. Our findings suggest a novel and distinct function of VEGF in mediating autocrine/intracrine CRC cell survival.

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Acknowledgements

We thank the Cytometry and Cellular Imaging Core Facility at M. D. Anderson Cancer Center (funded by NIH Cancer Center Support Grant CA016672) for assistance with data analysis using the flow cytometers. We thank Sunita Patterson (Department of Scientific Publications) for manuscript editing and Rita Hernandez for editorial assistance. This work was supported by the RE ‘Bob’ Smith Fund for Cancer Research (SS), NIH grants CCSG CA016672, T32 CA09599 (PG), R01 CA112390 (LME), and the William C Liedtke Chair in Cancer Research.

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Authors and Affiliations

  1. Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    S Samuel, F Fan, L Xia & L M Ellis

  2. Division of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, FL, USA

    L H Dang

  3. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    P Gaur & L M Ellis

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  1. S Samuel
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Correspondence to L M Ellis.

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LM Ellis received honoraria from Genentech/Roche. The other authors declare no conflict of interest.

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Samuel, S., Fan, F., Dang, L. et al. Intracrine vascular endothelial growth factor signaling in survival and chemoresistance of human colorectal cancer cells. Oncogene 30, 1205–1212 (2011). https://doi.org/10.1038/onc.2010.496

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