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.
Original language | English |
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Pages (from-to) | 508-519 |
Number of pages | 12 |
Journal | Cell Reports |
Volume | 18 |
Issue number | 2 |
DOIs | |
State | Published - Jan 10 2017 |
Bibliographical note
Publisher Copyright:© 2017 The Author(s)
Keywords
- Par-4
- Rab8b
- apoptosis
- chloroquine
- metastasis-inhibition
- p53
- secretagogues
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology