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HAb18G/CD147 promotes pSTAT3-mediated pancreatic cancer development via CD44s.


ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 has failed clinically. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate the potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo.The expression of HAb18G/CD147, pSTAT3, and CD44s was determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 were assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot assay, immunofluorescence staining, immunoprecipitation, and in vivo tumor formation using loss or gain-of-function strategies.Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. Cyclophilin A (CyPA), a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147-dependent mechanisms. HAb18G/CD147 was associated and colocalized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high coexpression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer.We identified HAb18G/CD147 as a novel upstream activator of STAT3, which interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest that HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies.

SUBMITTER: Li L 

PROVIDER: S-EPMC3873783 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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HAb18G/CD147 promotes pSTAT3-mediated pancreatic cancer development via CD44s.

Li Ling L   Tang Wenhua W   Wu Xiaoqing X   Karnak David D   Meng Xiaojie X   Thompson Rachel R   Hao Xinbao X   Li Yongmin Y   Qiao Xiaotan T XT   Lin Jiayuh J   Fuchs James J   Simeone Diane M DM   Chen Zhi-Nan ZN   Lawrence Theodore S TS   Xu Liang L  

Clinical cancer research : an official journal of the American Association for Cancer Research 20131016 24


<h4>Purpose</h4>Signal transducer and activator of transcription 3 (STAT3) plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 has failed clinically. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate the potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo.<h4>Experimental design</h4>The expression of HAb18G/CD147, pSTAT3  ...[more]

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