Gankyrin is essential for hypoxia enhanced metastatic potential in breast cancer cells

Mol Med Rep. 2014 Mar;9(3):1032-6. doi: 10.3892/mmr.2013.1860. Epub 2013 Dec 12.

Abstract

Hypoxia, a critical regulator of tumor growth and metastasis, induces the transcriptional activation of several pathways involved in proliferation, migration and invasion. Gankyrin was found to be overexpressed, and also promoted the metastasis in breast cancer cells, which is also involved in the regulation of hypoxia inducible factor‑1 and hypoxia‑inducible factor‑1α. The present study showed that gankyrin mRNA and protein expression were increased under hypoxic conditions in the BT474 breast cancer cell line, accompanied with increased ability of cell migration and invasion. Lentivirus‑mediated siRNA targeting gankyrin was transfected into BT474 cells. Wound‑healing and transwell experiments showed that gankyrin deletion abrogated the increased migration and invasion of BT474 cells due to hypoxia. In addition, E‑cadherin was found to be involved in the gankyrin induced invasion of breast cancer cells due to hypoxia. The present study indicated that gankyrin deletion abrogated the increased metastatic potential of breast cancer cells under hypoxic conditions partly through regulating E‑cadherin, suggesting that an improved understanding of gankyrin may offer a potential therapeutic target for the treatment of human breast cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / physiopathology*
  • Cadherins / metabolism
  • Cell Hypoxia*
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Humans
  • MCF-7 Cells
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism

Substances

  • Cadherins
  • PSMD10 protein, human
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Proteasome Endopeptidase Complex