KIFC1 regulates ZWINT to promote tumor progression and spheroid formation in colorectal cancer
KIFC1 regulates ZWINT to promote tumor progression and spheroid formation in colorectal cancer
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DOI：
10.1111/pin.13098
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发表时间：
2021-04-05
影响因子：
2.2
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
--
作者：
Akabane, Shintaro;Oue, Naohide;Yasui, Wataru
结直肠癌（CRC）是全球癌症相关死亡的第二大原因。驱动蛋白家族成员C1（KIFC 1）由于其在中心体聚集中介导癌细胞进展的关键作用而被认为是一个有前途的治疗靶点。本研究旨在分析KIFC 1在大肠癌中的表达及其生物学功能。免疫组化结果显示，129例结直肠癌患者中有67例（52%）KIFC 1阳性，与总生存率相关。与阴性对照细胞相比，KIFC 1小干扰RNA（siRNA）转染的细胞表现出较低的细胞增殖。一种特异性KIFC 1抑制剂，kolavenic acid类似物（KAA）可显著抑制CRC细胞增殖。微阵列分析显示，与对照细胞相比，KAA处理的CRC细胞呈现降低的ZW10相互作用动粒蛋白（ZWINT）表达。免疫组化结果显示，129例大肠癌中有61例（47%）ZWINT阳性，且ZWINT表达与KIFC 1表达显著相关。ZWINT阳性病例的总体生存率显著降低。KIFC 1 siRNA转染的细胞显示ZWINT表达减少，而ZWINT siRNA转染的细胞减少细胞增殖。KIFC 1和ZWINT敲减细胞均减弱球状体形成能力。这项研究为KIFC 1在CRC进展中调节ZWINT及其作为治疗靶点的潜力提供了新的见解。
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Kinesin Family Member C1 (KIFC1) has been proposed as a promising therapeutic target due to its pivotal role in centrosome clustering to mediate cancer cell progression. This study aimed to analyze the expression and biological function of KIFC1 in CRC. Immunohistochemically, 67 (52%) of 129 CRC cases were positive for KIFC1 and statistically associated with poorer overall survival. KIFC1 small interfering RNA (siRNA)-transfected cells demonstrated lower cell proliferation as compared to the negative control cells. A specific KIFC1 inhibitor, kolavenic acid analog (KAA) drastically inhibited CRC cell proliferation. Microarray analysis revealed that KAA-treated CRC cells presented reduced ZW10 interacting kinetochore protein (ZWINT) expression as compared to control cells. Immunohistochemical analysis demonstrated that 61 (47%) of 129 CRC cases were positive for ZWINT and ZWINT expression was significantly correlated with KIFC1 expression. ZWINT-positive cases exhibited significantly worse overall survival. KIFC1 siRNA-transfected cells showed reduced ZWINT expression while ZWINT siRNA-transfected cells decreased cell proliferation. Both KIFC1 and ZWINT knockdown cells attenuated spheroid formation ability. This study provides new insights into KIFC1 regulating ZWINT in CRC progression and its potential as a therapeutic target.