Orai1 and STIM1 are critical for breast tumor cell migration and metastasis

Cancer Cell. 2009 Feb 3;15(2):124-34. doi: 10.1016/j.ccr.2008.12.019.

Abstract

Tumor metastasis is the primary cause of death of cancer patients. Understanding the molecular mechanisms underlying tumor metastasis will provide potential drug targets. We report here that Orai1 and STIM1, both of which are involved in store-operated calcium entry, are essential for breast tumor cell migration in vitro and tumor metastasis in mice. Reduction of Orai1 or STIM1 by RNA interference in highly metastatic human breast cancer cells or treatment with a pharmacological inhibitor of store-operated calcium channels decreased tumor metastasis in animal models. Our data demonstrate a role for Orai1 and STIM1 in tumor metastasis and suggest store-operated calcium entry channels as potential cancer therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / physiopathology
  • Calcium / metabolism
  • Calcium Channel Blockers / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Female
  • Focal Adhesions / metabolism
  • Humans
  • Imidazoles / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis* / pathology
  • Neoplasm Metastasis* / physiopathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Transplantation
  • ORAI1 Protein
  • RNA Interference
  • Stromal Interaction Molecule 1
  • rac GTP-Binding Proteins / metabolism
  • ras GTPase-Activating Proteins / metabolism

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Imidazoles
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • Orai1 protein, mouse
  • STIM1 protein, human
  • Stim1 protein, mouse
  • Stromal Interaction Molecule 1
  • ras GTPase-Activating Proteins
  • rac GTP-Binding Proteins
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Calcium