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

Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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.

Original languageEnglish
Pages (from-to)508-519
Number of pages12
JournalCell Reports
Issue number2
StatePublished - Jan 10 2017

Bibliographical note

Funding Information:
This work was supported by NIH/NCI grants R01 CA165469, R01 CA187273, and R21 CA179283 (to V.M.R.). D.S.W. was supported by grant P30 RR020171 from the NIGMS to L. Hersh. N.A. was supported by a scholarship (ID 13137-13-1) from Coordenação de Aperfeiçoamento Superior (CAPES), Brazil. J.S. was supported by NCI grant T32 CA165990 (to V.M.R.). We thank Jason Brandon, PhD, for participating in the mouse experiments.

Publisher Copyright:
© 2017 The Author(s)


  • Par-4
  • Rab8b
  • apoptosis
  • chloroquine
  • metastasis-inhibition
  • p53
  • secretagogues

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


Dive into the research topics of 'Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis'. Together they form a unique fingerprint.

Cite this