The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma

Our previous studies showed that overexpression of secreted protein acidic and rich in cysteine (SPARC) induced autophagy-mediated apoptosis in PNET cells. In the present study, we attempted to elucidate the molecular mechanisms and signaling cascades associated with SPARC overexpression in combinat...

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Main Authors:	SAILAJA, G.S., BHOOPATHI, PRAVEEN, GORANTLA, BHARATHI, CHETTY, CHANDRAMU, GOGINENI, VENKATESWARA RAO, VELPULA, KIRAN KUMAR, GONDI, CHRISTOPHER S., RAO, JASTI S.
Format:	Online
Language:	English
Published:	D.A. Spandidos 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538858/

id	pubmed-3538858
recordtype	oai_dc
spelling	pubmed-35388582013-01-08 The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma SAILAJA, G.S. BHOOPATHI, PRAVEEN GORANTLA, BHARATHI CHETTY, CHANDRAMU GOGINENI, VENKATESWARA RAO VELPULA, KIRAN KUMAR GONDI, CHRISTOPHER S. RAO, JASTI S. Articles Our previous studies showed that overexpression of secreted protein acidic and rich in cysteine (SPARC) induced autophagy-mediated apoptosis in PNET cells. In the present study, we attempted to elucidate the molecular mechanisms and signaling cascades associated with SPARC overexpression in combination with radiation therapy that eventually leads to autophagy-mediated apoptosis in neuroblastoma. SPARC expression in SK-N-AS and NB-1691 cells demonstrated the activation of caspase 3, cleavage of PARP and induction of apoptosis. The experiments to unravel the mechanisms associated with autophagy-apoptosis illustrated that SPARC overexpression triggered endoplasmic reticulum (ER) stress and thereby unfolded protein response (UPR). This was apparent with the activation of stress receptors, inositol-requiring enzyme (IRE 1α), RNA-dependent protein kinase (PKR)-like ER kinase (PERK) and BiP. This study further demonstrated the induction of transcription factor CHOP as a result of IRE-JNK activation in response to increased SPARC levels. Inhibition of ER stress and JNK activation led to inhibition of autophagy-mediated apoptosis. Further, the apparent expression of ER stress molecules among the orthotopic tumors treated by SPARC overexpression plasmids substantiated our in vitro observations. Taken together, these results illustrate the critical role of ER stress in regulating autophagy-mediated apoptosis in SPARC-overexpressed neuroblastoma cells and radiation treatment. D.A. Spandidos 2012-10-24 /pmc/articles/PMC3538858/ /pubmed/23123816 http://dx.doi.org/10.3892/ijo.2012.1678 Text en Copyright © 2013, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	SAILAJA, G.S. BHOOPATHI, PRAVEEN GORANTLA, BHARATHI CHETTY, CHANDRAMU GOGINENI, VENKATESWARA RAO VELPULA, KIRAN KUMAR GONDI, CHRISTOPHER S. RAO, JASTI S.
spellingShingle	SAILAJA, G.S. BHOOPATHI, PRAVEEN GORANTLA, BHARATHI CHETTY, CHANDRAMU GOGINENI, VENKATESWARA RAO VELPULA, KIRAN KUMAR GONDI, CHRISTOPHER S. RAO, JASTI S. The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma
author_facet	SAILAJA, G.S. BHOOPATHI, PRAVEEN GORANTLA, BHARATHI CHETTY, CHANDRAMU GOGINENI, VENKATESWARA RAO VELPULA, KIRAN KUMAR GONDI, CHRISTOPHER S. RAO, JASTI S.
author_sort	SAILAJA, G.S.
title	The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma
title_short	The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma
title_full	The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma
title_fullStr	The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma
title_full_unstemmed	The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma
title_sort	secreted protein acidic and rich in cysteine (sparc) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma
description	Our previous studies showed that overexpression of secreted protein acidic and rich in cysteine (SPARC) induced autophagy-mediated apoptosis in PNET cells. In the present study, we attempted to elucidate the molecular mechanisms and signaling cascades associated with SPARC overexpression in combination with radiation therapy that eventually leads to autophagy-mediated apoptosis in neuroblastoma. SPARC expression in SK-N-AS and NB-1691 cells demonstrated the activation of caspase 3, cleavage of PARP and induction of apoptosis. The experiments to unravel the mechanisms associated with autophagy-apoptosis illustrated that SPARC overexpression triggered endoplasmic reticulum (ER) stress and thereby unfolded protein response (UPR). This was apparent with the activation of stress receptors, inositol-requiring enzyme (IRE 1α), RNA-dependent protein kinase (PKR)-like ER kinase (PERK) and BiP. This study further demonstrated the induction of transcription factor CHOP as a result of IRE-JNK activation in response to increased SPARC levels. Inhibition of ER stress and JNK activation led to inhibition of autophagy-mediated apoptosis. Further, the apparent expression of ER stress molecules among the orthotopic tumors treated by SPARC overexpression plasmids substantiated our in vitro observations. Taken together, these results illustrate the critical role of ER stress in regulating autophagy-mediated apoptosis in SPARC-overexpressed neuroblastoma cells and radiation treatment.
publisher	D.A. Spandidos
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538858/
_version_	1611945035130994688

The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma

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