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Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy
| Content Provider | Semantic Scholar |
|---|---|
| Author | Li, Bin Xu, Wen Wen Lam, Alfred King-Yin Wang, Yang Hu, Hui-fang Guan, Xin-Yuan Qin, Yan Ru Saremi, Nassim Tsao, Sai Wah He, Qingyu Cheung, Annie L. M. |
| Copyright Year | 2017 |
| Abstract | Metastasis is the most lethal hallmark of esophageal squamous cell carcinoma (ESCC). The aim of the study is to identify key signaling pathways that control metastasis in ESCC. Highly invasive ESCC sublines (designated I3 cells) were established through three rounds of selection of cancer cells invading through matrigel-coated chambers. Gene expression profile of one of the I3 sublines was compared with that of its parental cell line using cDNA microarray analysis. Gene ontology and pathway analyses of the differentially expressed genes (both upregulated and downregulated) indicated that genes associated with cellular movement and the AKT pathway were associated with increased cancer cell invasiveness. Western blot analysis confirmed increased phosphorylated AKT (p-AKT), N-cadherin and decreased E-cadherin expression in the I3 cells. Immunohistochemistry was used to evaluate the clinical significance of p-AKT expression in ESCC, and the results showed higher p-AKT nuclear expression in lymph node metastases when compared with primary carcinoma. Inactivation of the PI3K/AKT pathway with specific inhibitors, or with PTEN overexpression, resulted in reversed cadherin switching and inhibited cancer cell motility. Inhibition of the pathway by treatment with wortmannin markedly suppressed experimental metastasis in nude mice. Our data demonstrated the importance of the PI3K/AKT signaling pathway in ESCC metastasis and support PI3K/AKT as a valid therapeutic target in treatment of metastatic ESCC. |
| Starting Page | 38755 |
| Ending Page | 38766 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://hub.hku.hk/bitstream/10722/242110/1/content.pdf |
| Alternate Webpage(s) | http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=16333&path%5B%5D=52245 |
| PubMed reference number | 28418888 |
| Alternate Webpage(s) | https://doi.org/10.18632/oncotarget.16333 |
| DOI | 10.18632/oncotarget.16333 |
| Journal | Oncotarget |
| Volume Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anatomic Node Cadherins DNA, Complementary Keratinized squamous cell of esophagus Leukemia, B-Cell Metastatic Neoplasm Mice, Nude Ontology Para-aortic node Primary Carcinoma Proto-Oncogene Proteins c-akt Signal Transduction Pathways Squamous Epithelial Cells Squamous cell carcinoma of esophagus cancer cell lymph nodes matrigel negative regulation of Notch signaling pathway involved in somitogenesis wortmannin |
| Content Type | Text |
| Resource Type | Article |
