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World Journal of Surgical Oncology

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Open Access 01-12-2014 | Research

Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors

Authors: Kai-Hsi Hsu, Hung-Wen Tsai, Pin-Wen Lin, Yun-Shang Hsu, Pei-Jung Lu, Yan-Shen Shan

Published in: World Journal of Surgical Oncology | Issue 1/2014

Abstract

Background

Osteopontin (OPN) is a secreted phosphoprotein expressed by neoplastic cells involved in the malignant potential and aggressive phenotypes of human malignancies, including gastrointestinal stromal tumors (GISTs). Our previous study showed that OPN can promote tumor cell proliferation in GISTs. In this series, we further aim to investigate the effect of OPN on apoptosis in GISTs.

Methods

The expression of apoptotic and anti-apoptotic proteins in response to OPN was evaluated. In vitro effects of OPN against apoptosis in GIST were also assessed. GIST specimens were also used for analyzing protein expression of specific apoptosis-related molecules and their clinicopathologic significance.

Results

Up-regulation of β-catenin and anti-apoptotic proteins Mcl-1 with concomitant suppression of apoptotic proteins in response to OPN was noted. A significant anti-apoptotic effect of OPN on imatinib-induced apoptosis was identified. Furthermore, Mcl-1 overexpression was significantly associated with OPN and β-catenin expression in tumor tissues, as well as worse survival clinically.

Conclusions

Our study identifies anti-apoptotic effects of OPN that, through β-catenin-mediated Mcl-1 up-regulation, significantly antagonized imatinib-induced apoptosis in GISTs. These results provide a potential rationale for therapeutic strategies targeting both OPN and Mcl-1 of the same anti-apoptotic signaling pathway, which may account for resistance to imatinib in GISTs.

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Title: Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors
Authors: Kai-Hsi Hsu
Hung-Wen Tsai
Pin-Wen Lin
Yun-Shang Hsu
Pei-Jung Lu
Yan-Shen Shan
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2014
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/1477-7819-12-189

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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