Expression of carbonic anhydrase IX is associated with poor prognosis through regulation of the epithelial-mesenchymal transition in hepatocellular carcinoma
| العنوان: | Expression of carbonic anhydrase IX is associated with poor prognosis through regulation of the epithelial-mesenchymal transition in hepatocellular carcinoma |
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| المؤلفون: | Koichi Kawamoto, Satoshi Hyuga, Yutaka Takeda, Kunihito Gotoh, Hidetoshi Eguchi, Hiroshi Wada, Masahiro Tanemura, Yoshifumi Iwgami, Toru Otsuru, Daisaku Yamada, Masaki Mori, Koji Umeshita, Yuichiro Doki, Tadafumi Asaoka, Takehiro Noda |
| المصدر: | International Journal of Oncology. 51:1179-1190 |
| بيانات النشر: | Spandidos Publications, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Cancer Research, Small interfering RNA, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Cell Growth Processes, Biology, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Antigens, Neoplasm, Cell Line, Tumor, Carcinoma, medicine, Humans, Epithelial–mesenchymal transition, Carbonic Anhydrase IX, Aged, Aged, 80 and over, Oncogene, Liver Neoplasms, Hep G2 Cells, Middle Aged, Carbonic Anhydrase 9, Cell cycle, Cadherins, medicine.disease, Molecular medicine, Cell Hypoxia, 030104 developmental biology, Oncology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Disease Progression, Cancer research, Female |
| الوصف: | Carbonic anhydrase 9 (CA9) is a plasma membrane-associated isoenzyme that catalyzes pH regulation under hypoxic conditions. CA9 is transcriptionally regulated by hypoxia-inducible factor 1. Recent studies reported that hypoxia also promoted the epithelial-mesenchymal transition (EMT) in various cancers. In the present study, we evaluated the relationship between CA9 expression and EMT in vitro with two hepatoma cell lines. We also examined the clinical significance of CA9 expression in 117 consecutive patients that underwent hepatectomies for hepatocellular carcinoma (HCC). We evaluated CA9 expression and EMT induction under hypoxia with quantitative RT-PCR, western blot analysis and immunofluorescence staining, in HuH7 and HepG2 cells. We knocked down CA9 expression with small interfering RNA to evaluate the relationship between CA9 and EMT. We found that hypoxia induced CA9 expression in HCC cells and promoted EMT, evidenced by a loss of E-cadherin and an increase in N-cadherin. Twist, a transcriptional regulator of EMT, was also upregulated with hypoxia. The CA9 deficiency attenuated hypoxia-induced changes in E-cadherin and N-cadherin. Immunohistochemical evaluations of patient samples showed that CA9 was expressed in 50.4% of patients (59/117). However, patients with and without CA9 expression were not significantly different in clinicopathological factors. Nevertheless, a multivariate analysis showed that CA9 expression was an independent factor for both recurrence and prognosis among patients that underwent curative surgery for HCC. In conclusion, this study revealed that CA9 expression was a pivotal predictive factor for poor prognosis after radical surgery for HCC. Moreover, the CA9 regulation of the expression of EMT-related molecules represented a mechanism that enhanced malignant potential. |
| تدمد: | 1791-2423 1019-6439 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a13c29ede80aadb2619b0b0bb5017dd https://doi.org/10.3892/ijo.2017.4098 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0a13c29ede80aadb2619b0b0bb5017dd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17912423 10196439 |
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