American Association for Cancer Research
10780432ccr130621-sup-fig4.pdf (263.52 kB)

Supplementary Figure 4 from HAb18G/CD147 Promotes pSTAT3-Mediated Pancreatic Cancer Development via CD44s

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journal contribution
posted on 2023-03-31, 17:08 authored by Ling Li, Wenhua Tang, Xiaoqing Wu, David Karnak, Xiaojie Meng, Rachel Thompson, Xinbao Hao, Yongmin Li, Xiaotan T. Qiao, Jiayuh Lin, James Fuchs, Diane M. Simeone, Zhi-Nan Chen, Theodore S. Lawrence, Liang Xu

PDF file - 263K, The effects of HAb18G/CD147 promoting pancreatic tumor development are confirmed with pGIPZ and pTRIPZ CD147 shRNA (related to Figure 1).



Purpose: 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.Experimental Design: 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.Results: 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.Conclusions: 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. Clin Cancer Res; 19(24); 6703–15. ©2013 AACR.

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