Lysyl oxidase is induced by cell density-mediated cell cycle suppression via RB-E2F1-HIF-1α axis

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7 Citations (Scopus)

Abstract

Remodeling of the matrix surrounding tumor cells plays a crucial role in the development and maintenance of cancer. Lysyl oxidase (LOX), a matrix remodeling factor, is induced by HIF-1α under hypoxic conditions and associated with tumor growth and metastasis. Here, we report that high cell density induces HIF-1α expression under normoxic condition, resulting in the promotion of LOX expression. This phenomenon was observed in the retinoblastoma tumor suppressor (RB)-proficient breast cancer cells but not in RB-deficient cells. In RB-proficient cancer cells, the cell cycle regulator E2F1 was down-regulated and cell cycle progression was inhibited at high density culture condition. Knockdown of E2F1 stabilized HIF-1α and promoted LOX expression, while knockdown of both E2F1 and HIF-1α prevented the up-regulation of LOX. These findings suggest that elevated cell density enhances cell cycle arrest and matrix remodeling via RB-E2F1-HIF-1α axis.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalCell structure and function
Volume38
Issue number1
DOIs
Publication statusPublished - 2013 Jan 24

Keywords

  • Breast cancer
  • Cell cycle
  • Cell density
  • E2F1
  • Lysyl oxidase

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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