Down-regulation of DLC1 in endothelial cells compromises the angiogenesis process

Yi Ping Shih, Sarah Y. Yuan, Su Hao Lo

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

DLC1 is a RhoGAP-containing tumor suppressor that inhibits angiogenesis by repressing VEGF production in epithelial cells. Here we report the roles of DLC1 in endothelial cells. Silencing of DLC1 (siDLC1) enhances cell migration but reduces tube formation activities of human umbilical vein endothelial cells (HUVECs). Biochemically, RhoA activity and paxillin protein level are markedly increased in siDLC1 HUVECs. Although further silencing of RhoA restores the cell migration phenotype, the tube formation defect and up-regulated paxillin level remain unchanged. On the other hand, paxillin knockdown rescues tube formation and migration phenotypes but not the up-regulated RhoA activity. These results indicate that DLC1 regulates endothelial cell migration through RhoA and paxillin independently and controls tube formation mainly via paxillin. To further determine endothelial DLC1's function, we have generated endothelial specific knockout mice (DLC1-Tek). DLC1-Tek mice appear to be normal and healthy but their angiogenesis processes are compromised as shown in gel plug and aortic ring sprouting assays. Analysis of endothelial cells isolated from DLC1-Tek mice has further affirmed the cellular and biochemical phenotypes established in siDLC1 HUVECs. Our studies have demonstrated a positive regulatory role of endothelial DLC1 in angiogenesis.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalCancer Letters
Volume398
DOIs
StatePublished - Jul 10 2017
Externally publishedYes

Fingerprint

Paxillin
Down-Regulation
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Cell Movement
Phenotype
Knockout Mice
Vascular Endothelial Growth Factor A
Gels
Epithelial Cells
Neoplasms
Proteins

Keywords

  • Angiogenesis
  • DLC1
  • Focal adhesion
  • Paxillin
  • RhoA
  • Tube formation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Down-regulation of DLC1 in endothelial cells compromises the angiogenesis process. / Shih, Yi Ping; Yuan, Sarah Y.; Lo, Su Hao.

In: Cancer Letters, Vol. 398, 10.07.2017, p. 46-51.

Research output: Contribution to journalArticle

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