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KIF14 促进肿瘤进展和转移,是人类胃癌不良预后的独立预测因子。

KIF14 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in human gastric cancer.

机构信息

Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2019 Jan;1865(1):181-192. doi: 10.1016/j.bbadis.2018.10.039. Epub 2018 Nov 4.

Abstract

The kinesin family member 14 (KIF14) is a potential oncogene and is involved in the metastasis of various cancers. Nevertheless, its function in gastric cancer (GC) remains poorly defined. The expression of KIF14 was examined in GC cell lines and a clinical cohort of GC specimens by qPCR, western blotting and immunohistochemistry (IHC) staining. The relationship between KIF14 expression and the clinicopathological features was analyzed. The effect of KIF14 on cell proliferation, colony formation, invasion and migration were investigated in vitro and in vivo. The expression of KIF14 was significantly increased in the GC tissues and cell lines. High KIF14 expression was associated with tumor stage, tumor-node-metastasis (TNM) stage and metastasis. KIF14 was an independent prognostic factor for the overall survival of GC, and a higher expression of KIF14 predicted a poorer survival. KIF14 silencing resulted in attenuated proliferation, invasion and migration in human gastric cancer cells, whereas KIF14 ectopic expression facilitated these biological abilities. Notably, the depressed expression of KIF14 inhibited Akt phosphorylation, while overexpressed KIF14 augmented Akt phosphorylation. Additionally, there was a significant correlation between the expression of KIF14 and p‑Akt in GC tissues. Importantly, the proliferation, invasion and migration of the GC cells, which was promoted by KIF14 overexpression, was abolished by the Akt inhibitor MK-2206, while Akt overexpression greatly rescued the effects induced by KIF14 knockdown. Our findings are the first to demonstrate that KIF14 is overexpressed in GC, is correlated with poor prognosis and plays a crucial role in the progression and metastasis of GC.

摘要

驱动蛋白家族成员 14(KIF14)是一种潜在的癌基因,参与多种癌症的转移。然而,其在胃癌(GC)中的功能仍未得到明确界定。通过 qPCR、western blot 和免疫组织化学(IHC)染色检测 KIF14 在 GC 细胞系和 GC 临床标本中的表达。分析 KIF14 表达与临床病理特征的关系。在体外和体内研究 KIF14 对细胞增殖、集落形成、侵袭和迁移的影响。KIF14 在 GC 组织和细胞系中的表达明显增加。KIF14 高表达与肿瘤分期、肿瘤-淋巴结-转移(TNM)分期和转移有关。KIF14 是 GC 总生存的独立预后因素,高表达 KIF14 预示着生存较差。KIF14 沉默导致人胃癌细胞增殖、侵袭和迁移能力减弱,而过表达 KIF14 则促进这些生物学能力。值得注意的是,KIF14 表达下调抑制 Akt 磷酸化,而过表达 KIF14 则增强 Akt 磷酸化。此外,GC 组织中 KIF14 表达与 p-Akt 之间存在显著相关性。重要的是,KIF14 过表达促进的 GC 细胞增殖、侵袭和迁移,被 Akt 抑制剂 MK-2206 所抑制,而过表达 Akt 则大大挽救了由 KIF14 敲低引起的作用。我们的研究结果首次证明 KIF14 在 GC 中过表达,与不良预后相关,并在 GC 的进展和转移中发挥关键作用。

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