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Discovery of NKCC1 as a potential therapeutic target to inhibit hepatocellular carcinoma cell growth and metastasis
| Content Provider | Semantic Scholar |
|---|---|
| Author | Zhou, Yaya Sun, Wei Chen, Ning Xu, Chen Wang, Xinxin Dong, Kun Zhang, Binxue Zhang, Jian Ming Hao, Ning Sun, Aihua Wei, Handong He, Fuchu Jiang, Ying |
| Copyright Year | 2017 |
| Abstract | Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion. Knockdown of NKCC1 via RNA interference reduced HCC cell proliferation and invasion abilities in vitro and in vivo, whereas over-expression of NKCC1 significantly increased HCC cell proliferation and invasion abilities in vitro and in vivo. Additionally, blocking NKCC1 activity with bumetanide attenuated the proliferation and invasion abilities of HCC cells in vitro and limited the HCC growth in vivo. Further results suggested that NKCC1 promotes the invasion ability via MMP-2 activity, and that the WNK1/OSR1/NKCC1 signal pathway might play roles in HCC metastasis. For the first time, our study demonstrated that NKCC1 plays a role in HCC metastasis, and could be served as a potential target to inhibit HCC cell growth and metastasis. |
| Starting Page | 66328 |
| Ending Page | 66342 |
| Page Count | 15 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=20240&path%5B%5D=64540 |
| PubMed reference number | 29029515v1 |
| Alternate Webpage(s) | https://doi.org/10.18632/oncotarget.20240 |
| DOI | 10.18632/oncotarget.20240 |
| Journal | Oncotarget |
| Volume Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Bumetanide Cell Proliferation Cultured Cell Line Leukemia, B-Cell Liver carcinoma Membrane Proteins Metastatic Neoplasm Patients Plasma membrane RNA Interference Role Playing DIsorder SLC12A2 gene SLC12A2 wt Allele Sodium Sodium-Potassium-Chloride Symporters |
| Content Type | Text |
| Resource Type | Article |
