Systemic Par-4 inhibits non-autochthonous tumor growth

Yanming Zhao; Ravshan Burikhanov; Jason Brandon; Shirley Qiu; Brent J. Shelton; Brett Spear; Subbarao Bondada; Scott Bryson; Vivek M. Rangnekar

doi:10.4161/cbt.12.2.15734

Systemic Par-4 inhibits non-autochthonous tumor growth

Yanming Zhao
, Ravshan Burikhanov
, Jason Brandon
, Shirley Qiu
, Brent J. Shelton
, Brett Spear
, Subbarao Bondada
, Scott Bryson
, Vivek M. Rangnekar

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SA C domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SA C has not been validated in animal models. We show that Par-4/SA C-transgenic mice express systemic Par-4/SA C protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SA C pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SA C protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SA C is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.

Original language	English
Pages (from-to)	152-157
Number of pages	6
Journal	Cancer Biology and Therapy
Volume	12
Issue number	2
DOIs	https://doi.org/10.4161/cbt.12.2.15734
State	Published - Jul 15 2011

Bibliographical note

Funding Information:
This study was supported by KLCR grant, NIH/ NCI grants CA060872, CA105453 and CA116658 (to V.M.R.).

Funding

This study was supported by KLCR grant, NIH/ NCI grants CA060872, CA105453 and CA116658 (to V.M.R.).

Funders	Funder number
KLCR
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	CA105453, R01CA116658, CA060872

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Metastasis
Par-4
Systemic protein

ASJC Scopus subject areas

Molecular Medicine
Oncology
Pharmacology
Cancer Research

Access to Document

10.4161/cbt.12.2.15734

Cite this

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title = "Systemic Par-4 inhibits non-autochthonous tumor growth",

abstract = "The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SA C domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SA C has not been validated in animal models. We show that Par-4/SA C-transgenic mice express systemic Par-4/SA C protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SA C pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SA C protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SA C is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.",

keywords = "Metastasis, Par-4, Systemic protein",

author = "Yanming Zhao and Ravshan Burikhanov and Jason Brandon and Shirley Qiu and Shelton, \{Brent J.\} and Brett Spear and Subbarao Bondada and Scott Bryson and Rangnekar, \{Vivek M.\}",

note = "Funding Information: This study was supported by KLCR grant, NIH/ NCI grants CA060872, CA105453 and CA116658 (to V.M.R.).",

year = "2011",

month = jul,

day = "15",

doi = "10.4161/cbt.12.2.15734",

language = "English",

volume = "12",

pages = "152--157",

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T1 - Systemic Par-4 inhibits non-autochthonous tumor growth

AU - Zhao, Yanming

AU - Burikhanov, Ravshan

AU - Brandon, Jason

AU - Qiu, Shirley

AU - Shelton, Brent J.

AU - Spear, Brett

AU - Bondada, Subbarao

AU - Bryson, Scott

AU - Rangnekar, Vivek M.

N1 - Funding Information: This study was supported by KLCR grant, NIH/ NCI grants CA060872, CA105453 and CA116658 (to V.M.R.).

PY - 2011/7/15

Y1 - 2011/7/15

N2 - The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SA C domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SA C has not been validated in animal models. We show that Par-4/SA C-transgenic mice express systemic Par-4/SA C protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SA C pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SA C protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SA C is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.

AB - The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SA C domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SA C has not been validated in animal models. We show that Par-4/SA C-transgenic mice express systemic Par-4/SA C protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SA C pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SA C protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SA C is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.

KW - Metastasis

KW - Par-4

KW - Systemic protein

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DO - 10.4161/cbt.12.2.15734

M3 - Article

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AN - SCOPUS:79960408944

SN - 1538-4047

VL - 12

SP - 152

EP - 157

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

IS - 2

ER -

Systemic Par-4 inhibits non-autochthonous tumor growth

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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