KIF18B promotes tumor progression in osteosarcoma by activating β-catenin
KIF18B promotes tumor progression in osteosarcoma by activating β-catenin
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KIF18B 通过激活 β-catenin 促进骨肉瘤的肿瘤进展
DOI：
10.20892/j.issn.2095-3941.2019.0452
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发表时间：
2020-05-01
影响因子：
5.5
通讯作者：
Fan, Zhengfu
中科院分区：
文献类型：
--
作者：
Gao, Tian;Yu, Ling;Fan, Zhengfu
目的：骨肉瘤是一种常见的原发高度恶性骨肿瘤。Kinesin家族成员18B(KIF18B)是一种潜在的癌基因，参与多种癌症的发生和转移。虽然KIF18B在骨肉瘤组织中的过度表达已被明确检测到，但其在疾病过程中的特定功能仍有待确定。此外，我们还研究了KIF18B在体外和体内对骨肉瘤细胞增殖、迁移和侵袭的影响。结果：KIF18B在骨肉瘤组织和细胞中过表达。KIF18B基因敲除可诱导骨肉瘤细胞周期停滞于G1/S期，显著抑制骨肉瘤细胞的增殖、迁移和侵袭。KIF18B通过控制ATF2的核聚集在转录水平调节β-连环蛋白的表达，并通过与骨肉瘤细胞中的腺瘤性息肉病(APC)抑癌基因相互作用在转录后水平调节β-连环蛋白的表达。结论：KIF18B通过减少ATF2的核聚集在转录水平调节β-连环蛋白的表达，或通过与APC的相互作用在转录后水平调节β-连环蛋白的表达，从而在骨肉瘤中发挥致癌作用。我们的集体发现支持KIF18B作为一种新的骨肉瘤预后生物标志物的潜在用途。
Objective: Osteosarcoma is a common primary highly malignant bone tumor. Kinesin family member 18B (KIF18B) has been identified as a potential oncogene involved in the development and metastasis of several cancer types. While KIF18B overexpression in osteosarcoma tissue is clearly detected, its specific function in the disease process remains to be established.Methods: KIF18B expression was assessed in osteosarcoma tissues and cells. We additionally evaluated the effects of KIF18B on proliferation, migration, and invasion of osteosarcoma cells, both in vitro and in vivo.Results: Our results showed overexpression of KIF18B in osteosarcoma tissues and cells. Knockdown of KIF18B induced G1/S phase arrest and significantly inhibited proliferation, migration, and invasion of osteosarcoma cells, both in vitro and in vivo. KIF18B regulated beta-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli (APC) tumor suppressor gene in osteosarcoma cells.Conclusions: KIF18B plays a carcinogenic role in osteosarcoma by regulating expression of beta-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC. Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.