Open AccessInhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule‐targeting agents by blocking cytokinesis
Author(s) -
Liu Xinran,
Li Yangkai,
Zhang Xia,
Liu XinYuan,
Peng Anlin,
Chen Yuchen,
Meng Lijing,
Chen Hong,
Zhang Yu,
Miao Xiaoping,
Zheng Ling,
Huang Kun
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13794
Subject(s) - cytokinesis , kinesin , mitosis , microtubule , cancer research , telophase , metaphase , biology , cell cycle , microbiology and biotechnology , cell , cell division , genetics , anaphase , gene , chromosome
Abstract Kinesin family member 20B ( KIF 20B, also known as MPHOSPH 1) is a kinesin protein that plays a critical role in cytokinesis. Previously, we and others have demonstrated the oncogenic role of KIF 20B in several cancers; however, the exact mechanisms underlying its tumorigenic effects remain unclear. Herein, we showed overexpression of KIF 20B in human hepatocellular carcinoma ( HCC ) and reported a negative correlation between KIF 20B level and prognosis of patients. Mechanistically, reducing KIF 20B blockades mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent way. Importantly, reducing KIF 20B acts synergistically with three microtubule‐associated agents ( MTA ) to p53‐ or p14 ARF ‐dependently suppress p53‐wt or p53‐null HCC cells. In addition to taxol, reducing KIF 20B also enhanced the toxicity of two chemotherapeutic drugs, hydroxycamptothecin and mitomycin C. In conclusion, we found a novel mechanism in that blocking cytokinesis by KIF 20B inhibition increases the efficacy of MTA ; our results thus suggested a dual‐mitotic suppression approach against HCC by combining MTA with KIF 20B inhibition, which simultaneously blocks mitosis at both metaphase and telophase.