Li Yonghe, Lu Wenyan, Chen Dongquan, Boohaker Rebecca J, Zhai Ling, Padmalayam Indira, Wennerberg Krister, Xu Bo, Zhang Wei
a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
b Division of Preventive Medicine and Comprehensive Cancer Center; Department of Medicine; University of Alabama at Birmingham ; Birmingham , AL USA.
Cancer Biol Ther. 2015;16(9):1316-22. doi: 10.1080/15384047.2015.1070980. Epub 2015 Jul 15.
Kinesin-like protein KIFC1, a normally nonessential kinesin motor, plays a critical role in centrosome clustering in cancer cells and is essential for the survival of cancer cells. Herein, we reported that KIFC1 expression is up-regulated in breast cancer, particularly in estrogen receptor negative, progesterone receptor negative and triple negative breast cancer, and is not associated with epidermal growth factor receptor 2 status. In addition, KIFC1 is highly expressed in all 8 tested human breast cancer cell lines, but is absent in normal human mammary epithelial cells and weakly expressed in 2 human lung fibroblast lines. Moreover, KIFC1 silencing significantly reduced breast cancer cell viability. Finally, we found that PJ34, a potent small molecule inhibitor of poly(ADP-ribose) polymerase, suppressed KIFC1 expression and induced multipolar spindle formation in breast cancer cells, and inhibited cell viability and colony formation within the same concentration range, suggesting that KIFC1 suppression by PJ34 contributes to its anti-breast cancer activity. Together, these results suggest that KIFC1 is a novel promising therapeutic target for breast cancer.
驱动蛋白样蛋白KIFC1是一种通常非必需的驱动蛋白,在癌细胞的中心体聚集过程中发挥关键作用,并且对癌细胞的存活至关重要。在此,我们报告KIFC1在乳腺癌中表达上调,尤其是在雌激素受体阴性、孕激素受体阴性和三阴性乳腺癌中,且与表皮生长因子受体2状态无关。此外,KIFC1在所有8种测试的人乳腺癌细胞系中均高表达,但在正常人乳腺上皮细胞中不存在,在2种人肺成纤维细胞系中弱表达。而且,KIFC1沉默显著降低了乳腺癌细胞的活力。最后,我们发现聚(ADP - 核糖)聚合酶的强效小分子抑制剂PJ34抑制KIFC1表达并诱导乳腺癌细胞形成多极纺锤体,并且在相同浓度范围内抑制细胞活力和集落形成,这表明PJ34对KIFC1的抑制作用有助于其抗乳腺癌活性。总之,这些结果表明KIFC1是一种新型且有前景的乳腺癌治疗靶点。