Cancer-associated fibroblast-derived WNT5A promotes cell proliferation, metastasis, stemness and glycolysis in gastric cancer via regulating HK2.

IF 2.5 3区医学 Q3 ONCOLOGY

World Journal of Surgical Oncology Pub Date : 2024-07-25 DOI:10.1186/s12957-024-03482-7

Yongsu Xu, Zhengju Ren, Fang Zeng, Huan Yang, Chengju Hu

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引用次数: 0

Abstract

Background: Gastric cancer (GC) is one of the most common cancers worldwide. Tumor microenvironment plays an important role in tumor progression. This study aims to explore the role of cancer-associated fibroblasts (CAFs) in GC and the underlying mechanism.

Methods: Cell viability, proliferation, invasion and migration were assessed by MTT, EdU, transwell and wound healing assays, respectively. Sphere formation assay was used to evaluate cell stemness. Glucose consumption, lactate production and ATP consumption were measured to assess glycolysis. In addition, The RNA and protein expression were detected by qRT-PCR and western blot. The interaction between wingless Type MMTV Integration Site Family, Member 5 A (WNT5A) and hexokinase 2 (HK2) was verified by Co-immunoprecipitation. The xenograft model was established to explore the function of CAFs on GC tumor growth in vivo.

Results: CAFs promoted the proliferation, metastasis, stemness and glycolysis of GC cells. WNT5A was upregulated in CAFs, and CAFs enhanced WNT5A expression in GC cells. Knockdown of WNT5A in either GC cells or CAFs repressed the progression of GC cells. In addition, WNT5A promoted HK2 expression, and overexpression of HK2 reversed the effect of WNT5A knockdown in CAFs on GC cells. Besides, knockdown of WNT5A in CAFs inhibits tumor growth in vivo.

Conclusion: CAF-derived WNT5A facilitates the progression of GC via regulating HK2 expression.

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癌症相关成纤维细胞衍生的 WNT5A 通过调控 HK2 促进胃癌细胞增殖、转移、干细胞和糖酵解。

背景：胃癌（GC）是全球最常见的癌症之一：胃癌（GC）是全球最常见的癌症之一。肿瘤微环境在肿瘤进展中起着重要作用。本研究旨在探讨癌相关成纤维细胞（CAFs）在胃癌中的作用及其内在机制：方法：细胞活力、增殖、侵袭和迁移分别通过 MTT、EdU、transwell 和伤口愈合试验进行评估。球形成试验用于评估细胞干性。测量葡萄糖消耗、乳酸生成和 ATP 消耗以评估糖酵解。此外，还通过 qRT-PCR 和 Western 印迹检测了 RNA 和蛋白质的表达。通过共免疫沉淀验证了无翼型 MMTV 整合位点家族成员 5 A（WNT5A）与己糖激酶 2（HK2）之间的相互作用。建立了异种移植模型，以探讨CAFs对体内GC肿瘤生长的作用：结果：CAFs促进了GC细胞的增殖、转移、干性和糖酵解。WNT5A在CAFs中上调，CAFs增强了WNT5A在GC细胞中的表达。在 GC 细胞或 CAFs 中敲除 WNT5A 可抑制 GC 细胞的发展。此外，WNT5A 能促进 HK2 的表达，而 HK2 的过表达能逆转 CAF 中 WNT5A 基因敲除对 GC 细胞的影响。此外，敲除CAF中的WNT5A可抑制肿瘤在体内的生长：结论：CAF衍生的WNT5A通过调节HK2的表达促进GC的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Surgical Oncology ONCOLOGY-SURGERY

CiteScore

4.70

自引率

15.60%

发文量

362

审稿时长

3 months

期刊介绍： World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics. Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.

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