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

doi:10.1016/j.celrep.2016.12.051

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 journal › Article › peer-review

58 Scopus citations

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
Pages (from-to)	508-519
Number of pages	12
Journal	Cell Reports
Volume	18
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2016.12.051
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2016.12.051

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Burikhanov, R., Hebbar, N., Noothi, S. K., Shukla, N., Sledziona, J., Araujo, N., Kudrimoti, M., Wang, Q. J., Watt, D. S., Welch, D. R., Maranchie, J., Harada, A., & Rangnekar, V. M. (2017). Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis. Cell Reports, 18(2), 508-519. https://doi.org/10.1016/j.celrep.2016.12.051

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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.",

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AU - Shukla, Nidhi

AU - Sledziona, James

AU - Araujo, Nathália

AU - Kudrimoti, Meghana

AU - Wang, Qing Jun

AU - Watt, David S.

AU - Welch, Danny R.

AU - Maranchie, Jodi

AU - Harada, Akihiro

AU - Rangnekar, Vivek M.

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AB - 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.

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KW - Rab8b

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KW - metastasis-inhibition

KW - p53

KW - secretagogues

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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