HPIP is Upregulated in Liver Cancer and Promotes Hepatoma Cell Proliferation via Activation of G2/M Transition

HPIP is Upregulated in Liver Cancer and Promotes Hepatoma Cell Proliferation via Activation of G2/M Transition
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HPIP 在肝癌中表达上调,并通过激活 G2/M 转变促进肝癌细胞增殖

DOI:
10.1002/iub.1202
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发表时间:
2013-10-01
期刊:
影响因子:
4.6
通讯作者:
Ye, Qinong
Ye, Qinong
中科院分区:
生物学3区
文献类型:
--
作者:
Xu, Xiaojie;Jiang, Chengying;Ye, Qinong

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造血前 B 细胞白血病转录因子 (PBX) 相互作用蛋白 (HPIP) 已被证明在癌症的发生和进展中发挥作用。然而,HPIP在癌细胞生长中的详细作用以及HPIP调节癌细胞增殖的确切机制仍不清楚。在此,我们报告 HPIP 在 328 名肝癌患者中的大多数中过度表达,并通过 G2/M 检查点激活调节肝癌细胞增殖。 HPIP 增加了人肝癌细胞系的贴壁依赖性和非依赖性生长。 HPIP 的氨基酸区域 531-631 对于调节肝癌细胞生长非常重要。 HPIP 对肝癌细胞增殖的增强作用与 G2/M 细胞周期的激活以及细胞周期蛋白 B1 的显着增加和负 G2/M 期调节剂 GADD45 的抑制有关。 HPIP 敲除显着抑制了裸鼠中 HepG2 肝癌细胞的生长。这些数据强调了HPIP在肝癌细胞生长中的重要作用,并表明HPIP可能是肝癌治疗的良好靶标。 (c) 2013 IUBMB 生活,65(10):873-882,2013
Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) has been shown to play a role in cancer development and progression. However, the detailed role of HPIP in cancer cell growth and the exact mechanism by which HPIP regulates cancer cell proliferation remains unclear. Here, we report that HPIP is overexpressed in most of 328 liver cancer patients and regulates hepatoma cell proliferation through G2/M checkpoint activation. HPIP increased anchorage-dependent and -independent growth of human liver cancer cell lines. The amino acid region 531-631 of HPIP was important for its modulation of liver cancer cell growth. The increased effects of HPIP on liver cancer cell proliferation were associated with activation of the G2/M cell-cycle concomitant with a marked increase of cyclin B1 and the inhibition of the negative G2/M phase regulator GADD45. HPIP knockdown dramatically suppressed the growth of HepG2 liver cancer cells in nude mice. These data highlight the important role of HPIP in liver cancer cell growth and suggest that HPIP may be a good target for liver cancer therapy. (c) 2013 IUBMB Life, 65(10):873-882, 2013