HKDC1 上调促进糖酵解和疾病进展，并赋予胃癌化疗耐药性,Cancer Science

当前位置： X-MOL 学术 › Cancer Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

HKDC1 上调促进糖酵解和疾病进展，并赋予胃癌化疗耐药性
Cancer Science ( IF 4.5 ) Pub Date : 2022-12-15 , DOI: 10.1111/cas.15692
Mei-Qian Wang _{1,

2} , Yi-Ru Chen ₃ , Hui-Wen Xu ₁ , Jia-Rong Zhan ₂ , Da-Qin Suo ₂ , Ji-Jin Wang ₄ , Yuan-Zhen Ma ₂ , Xin-Yuan Guan _{2,

5} , Yan Li ₂ , Sen-Lin Zhu ₁

Affiliation

越来越多的证据表明己糖激酶参与细胞增殖和迁移。然而，含己糖激酶结构域的蛋白 1 (HKDC1) 在胃癌 (GC) 中的功能仍不清楚。使用免疫组织化学分析和大数据挖掘来评估 GC 中 HKDC1 表达与临床特征之间的相关性。此外，通过体外和体内试验研究了 HKDC1 在 GC 中的生物学功能和分子机制。我们的研究表明，与邻近的非肿瘤组织相比，HKDC1 表达在 GC 组织中上调。HKDC1 的高表达与较差的预后相关。功能实验表明，HKDC1 上调促进糖酵解、细胞增殖和肿瘤发生。此外，HKDC1 可通过诱导上皮-间质转化 (EMT) 来增强 GC 的侵袭和转移。HKDC1 的废除可有效减弱其致癌和转移功能。此外，HKDC1 在体内促进了 GC 增殖和迁移。HKDC1 过表达赋予 GC 细胞对顺铂、奥沙利铂和 5-氟尿嘧啶 (5-Fu) 的化学抗性。此外，核因子 kappa-B (NF-κB) 抑制剂 PS-341 可以减弱 GC 细胞中 HKDC1 过表达诱导的肿瘤发生、转移和耐药能力。我们的结果强调了 HKDC1 通过激活 NF-κB 通路在促进 GC 细胞的糖酵解、肿瘤发生和 EMT 方面的关键作用。此外，HKDC1 介导的耐药性与 DNA 损伤修复相关，进一步激活 NF-κB 信号。

"点击查看英文标题和摘要"

HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer

There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein-1 (HKDC1) in gastric cancer (GC) remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial–mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5-fluorouracil (5-Fu) onto GC cells. Furthermore, nuclear factor kappa-B (NF-κB) inhibitor PS-341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF-κB pathway. In addition, HKDC1-mediated drug resistance was associated with DNA damage repair, which further activated NF-κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.

更新日期：2022-12-15

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南