MPHOSPH1: A potential therapeutic target for hepatocellular carcinoma

Xinran Liu, Yafan Zhou, Xinyuan Liu, Anlin Peng, Hao Gong, Lizi Huang, Kaige Ji, Robert B. Petersen, Ling Zheng, Kun Huang

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)6623-6634
Number of pages12
JournalCancer Research
Volume74
Issue number22
DOIs
StatePublished - Nov 15 2014

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