Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis

Academic Article

Abstract

  • The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings indicate that CQ induces p53- and Rab8b-dependent Par-4 secretion from normal cells for Par-4-dependent inhibition of metastatic tumor growth.
  • Published In

  • Cell Reports  Journal
  • Digital Object Identifier (doi)

    Author List

  • Burikhanov R; Hebbar N; Noothi SK; Shukla N; Sledziona J; Araujo N; Kudrimoti M; Wang QJ; Watt DS; Welch DR
  • Start Page

  • 508
  • End Page

  • 519
  • Volume

  • 18
  • Issue

  • 2