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. Cancer Res; 74(22); 6623-34. Ó2014 AACR.
Bisphenols (BPs) are widely used in the production of plastic material, misfolded human islet amyloid polypeptide (hIAPP) is a causal factor in diabetes. We demonstrated BPs analogues show different effects on hIAPP amyloid formation.
<p>Supplementary Information: provides experimental procedures in details, as well as two tables and one figure. Table S1. Features and relative expression levels of MPHOSPH1 of clinical samples. Table S2. Hepatic function assays of the orthotopic HCC xenograft animal model. Figure S1. In vivo knockdown of endogenous MPHOSPH1 inhibits orthotopic HCC xenograft growth. Tumor nodules are indicated with yellow arrows.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.