the extra domain a of fibronectin increases vegf-c expression in colorectal carcinoma involving the pi3kakt signaling pathway纤连蛋白的额外的域增加vegf-c表达式在结直肠癌pi3kakt信号通路.pdfVIP

The Extra Domain A of Fibronectin Increases VEGF-C Expression in Colorectal Carcinoma Involving the PI3K/ AKT Signaling Pathway . . Lisha Xiang , Ganfeng Xie , Juanjuan Ou, Xing Wei, Feng Pan, Houjie Liang* Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Abstract The extra domain A (EDA)-containing fibronectin (EDA-FN), an alternatively spliced form of the extracellular matrix protein fibronectin, is predominantly expressed in various malignancies but not in normal tissues. In the present study, we investigated the potential pro-lymphangiogenesis effects of extra domain A (EDA)-mediated vascular endothelial growth factor-C (VEGF-C) secretion in colorectal carcinoma (CRC). We detected the expressions of EDA and VEGF-C in 52 human colorectal tumor tissues and their surrounding mucosae by immunohistochemical analysis, and further tested the correlation between the expressions of these two proteins in aforementioned CRC tissues. Both EDA and VEGF-C were abundantly expressed in the specimens of human CRC tissues. And VEGF-C was associated with increased expression of EDA in human CRC according to linear regression analysis. Besides, EDA expression was significantly correlated with lymph node metastasis, tumor differentiation and clinical stage by clinicopathological analysis of tissue microarrays containing tumor tissues of 115 CRC patients. Then, human CRC cell SW480 was transfected with lentivectors to elicit expression of shRNA against EDA (shRNA-EDA), and SW620 was transfected with a lentiviral vector to overexpress EDA (pGC-FU-EDA), respectively. We confirmed that VEGF-C was upregulated in EDA-overexpressed cells, and downregulated