胆管癌（CCA）是一种来自肝胆系统且致命性极高的癌症，其特征为侵袭性生长和早期淋巴转移。阐明其潜在机制并确定有效的治疗方法对于晚期CCA患者至关重要。在本研究中，我们发现KIF14在CCA样本中上调，尤其是在具有淋巴结转移和血管侵犯的患者中。高KIF14的CCA患者与手术后较差的总体生存率和无复发生存率相关。收益和失去功能研究表明，KIF14增强了CCA细胞的增殖、迁移、侵袭和淋巴转移能力，而其沉默则在体内外消除了其影响。机理研究表明，KIF14结合了G3BP1 / YBX1复合物并促进其相互作用，导致NF-κB启动子的活性增加和NF-κB通路的激活。此外，KIF14水平的增加增强了基于吉西他滨的化疗方案的药物抵抗力并诱导免疫抑制性微环境。此外，KIF14是HNF4A的直接靶点，并由HNF4A反向调节。综上所述，这些发现表明KIF14可能是一个潜在的癌基因，并且是预测CCA患者预后和化疗指导的良好指标。© 2023. 作者（们），在Springer Nature Limited的独家许可下。

Cholangiocarcinoma (CCA), a highly lethal and fetal cancer derived from the hepatobiliary system, is featured by aggressive growth and early lymphatic metastasis. Elucidating the underlying mechanism and identifying the effective therapy are critical for advanced CCA patients. In the study, we detected that KIF14 was upregulated in CCA samples, especially in patients with lymph node metastasis and vascular invasion. CCA patients with higher KIF14 were associated with worse overall survival and recurrence-free survival after surgery. Gain-of and loss-of function studies showed that KIF14 enhanced CCA cells proliferation, migration, invasion and lymphatic metastasis whereas its silencing abolished the effects in vivo and in vitro. Mechanistic investigation showed that KIF14 bound to the G3BP1/YBX1 complex and facilitated their interaction, causing increased activity of the NF-κB promoter and activation of NF-κB pathway. Furthermore, increased KIF14 level enhanced chemotherapy-resistance to gemcitabine-based regimen and induced immunosuppressive microenvironment. In addition, KIF14 was direct target of HNF4A and inversely regulated by HNF4A. Together, these findings suggested that KIF14 could be a potential oncogene and a good indicator in predicting prognosis and chemotherapy guidance for CCA patients.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.