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

Samson Mathews Samuel | Zendy; Fei Fan | Zendy; Long H. Dang | Zendy; Liangping Xia | Zendy; Puja Gaur | Zendy; Lee M. Ellis | Zendy

Open Access

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

Author(s) -

Samson Mathews Samuel,

Fei Fan,

Long H. Dang,

Liangping Xia,

Puja Gaur,

Lee M. Ellis

Publication year - 2010

Publication title -

oncogene

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.395

H-Index - 342

eISSN - 1476-5594

pISSN - 0950-9232

DOI - 10.1038/onc.2010.496

Subject(s) - intracrine , autocrine signalling , biology , survivin , cancer research , vascular endothelial growth factor , angiogenesis , paracrine signalling , vascular endothelial growth factor a , downregulation and upregulation , apoptosis , colorectal cancer , cell cycle , cell growth , cancer , medicine , cell culture , receptor , vegf receptors , gene , genetics , biochemistry

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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