Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2017-01, Vol.18 (2), p.508-519

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Chloroquine induces the secretion of the tumor suppressor protein Par-4•Chloroquine-induced Par-4 secretion depends on p53•p53 directly induces Rab8b expression critical for Par-4 secretion•Par-4 is essential for apoptosis and inhibition of tumor metastasis by chloroquine Burikhanov et al. identify the anti-malarial drug chloroquine (CQ) as a robust secretagogue of tumor suppressor Par-4. CQ-inducible Par-4 secretion is dependent on p53 and Rab8b for vesicle transport. Induction of Par-4 secretion provides an attractive option for the re-purposing of existing drugs for apoptosis and inhibition of tumor metastasis.