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

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

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)


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.

期刊World Journal of Surgical Oncology
出版狀態Published - 2014 六月 20

All Science Journal Classification (ASJC) codes

  • 手術
  • 腫瘤科


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