MPHOSPH1: A Potential Therapeutic Target for Hepatocellular Carcinoma
文献类型：期刊论文
| 作者 | Liu, XR; Zhou, YF; Liu, XY; Peng, AL; Gong, H; Huang, LZ; Ji, KG; Petersen, RB; Zheng, L; Huang, K |
| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2014 |
| 卷号 | 74期号:22页码:6623-6634 |
| 通讯作者 | Huang, K (reprint author), Huazhong Univ Sci & Technol, 13 Hang Kong Rd, Wuhan 430030, Peoples R China.,kunhuang2008@hotmail.com |
| 英文摘要 | MPHOSPH1 is a critical kinesin protein that functions in cytokinesis. Here, we show that MPHOSPH1 is overexpressed in hepatocellular carcinoma (HCC) cells, where it is essential for proliferation. Attenuating MPHOSPH1 expression with a tumor-selective shRNA-expressing adenovirus (Ad-shMPP1) was sufficient to arrest HCC cell proliferation in a manner associated with an accumulation of multinucleated polyploid cells, induction of postmitotic apoptosis, and increased sensitivity to taxol cytotoxicity. Mechanistic investigations showed that attenuation of MPHOSPH1 stabilized p53, blocked STAT3 phosphorylation, and prolonged mitotic arrest. In a mouse subcutaneous xenograft model of HCC, tumoral injection of Ad-shMPP1 inhibited MPHOSPH1 expression and tumor growth in a manner correlated with induction of apoptosis. Combining Ad-shMPP1 injection with taxol administration enhanced antitumor efficacy relative to taxol alone. Furthermore, Ad-shMPP1 tail vein injection suppressed formation of orthotopic liver nodules and prevented hepatic dysfunction. Taken together, our results identify MPHOSPH1 as an oncogenic driver and candidate therapeutic target in HCC. (C) 2014 AACR. |
| 学科主题 | Oncology |
| 类目[WOS] | Oncology |
| 关键词[WOS] | KINESIN-RELATED PROTEIN ; PHASE-II ; ANTITUMOR-ACTIVITY ; TUMOR-SUPPRESSOR ; ONCOGENIC ROLE ; BREAST-CANCER ; INHIBITION ; EXPRESSION ; ISPINESIB ; CELLS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000345130500024 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/264]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Liu, XR,Zhou, YF,Liu, XY,et al. MPHOSPH1: A Potential Therapeutic Target for Hepatocellular Carcinoma[J]. CANCER RESEARCH,2014,74(22):6623-6634. |
| APA | Liu, XR.,Zhou, YF.,Liu, XY.,Peng, AL.,Gong, H.,...&Huang, K.(2014).MPHOSPH1: A Potential Therapeutic Target for Hepatocellular Carcinoma.CANCER RESEARCH,74(22),6623-6634. |
| MLA | Liu, XR,et al."MPHOSPH1: A Potential Therapeutic Target for Hepatocellular Carcinoma".CANCER RESEARCH 74.22(2014):6623-6634. |
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