Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1α-mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma

Kin Wah Lee, Ronnie T.P. Poon, Anthony P. Yuen, Ming Tat Ling, Xiang Hong Wang, Yong Chuan Wong, Xin Yuan Guan, Kwan Man, Zao You Tang, Sheung Tat Fan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

61 Citations (Scopus)

Abstract

Purpose: Metastasis is commonly associated with poor prognosis of hepatocellular carcinoma (HCC). Being an important angiogenic factor, vascular endothelial growth factor (VEGF) plays a central role in HCC growth and metastasis. Recently, Id-1 (inhibitor of differentiation/DNA synthesis) has been suggested to be a key factor in cancer progression but the molecular mechanism remains unknown. Experimental Design: We first showed that overexpression of Id-1 was correlated with HCC metastasis (P < 0.001) and its expression was significantly correlated with VEGF expression by tissue microarray. By ectopic transfection of Id-1 into HCC cells, Id-1 was able to induce VEGF secretion through activation of VEGF transcription. Results: Increased VEGF secretion in Id-1 transfectants induced morphologic change and proliferation of human umbilical vascular endothelial cell resulting in promotion of angiogenesis. Id-1 induced transcriptional activation of VEGF by stabilizing hypoxia-inducible factor-1α protein. Down-regulation of Id-1 by antisense approach led to suppression of hypoxia-inducible factor-1α-mediated VEGF production. In addition, Id-1 suppression resulted in retardation of cell invasion through down-regulation of VEGF. Conclusions: Id-1 is a novel angiogenic factor for HCC metastasis and down-regulation of Id-1 may be a novel target to inhibit HCC metastasis through suppression of angiogenesis.
Original languageEnglish
Pages (from-to)6910-6919
Number of pages10
JournalClinical Cancer Research
Volume12
Issue number23
DOIs
Publication statusPublished - 1 Dec 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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