癌相关成纤维细胞衍生的 WNT5A 通过调节 HK2 促进胃癌细胞增殖、转移、干性和糖酵解。
Cancer-associated fibroblast-derived WNT5A promotes cell proliferation, metastasis, stemness and glycolysis in gastric cancer via regulating HK2.
机构信息
Nursing Department, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
School of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
出版信息
World J Surg Oncol. 2024 Jul 25;22(1):193. doi: 10.1186/s12957-024-03482-7.
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.
背景
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 GC 中的作用及其潜在机制。
方法
通过 MTT、EdU、transwell 和划痕愈合实验分别评估细胞活力、增殖、侵袭和迁移。球形成实验用于评估细胞干性。通过测量葡萄糖消耗、乳酸生成和 ATP 消耗来评估糖酵解。此外，通过 qRT-PCR 和 Western blot 检测 RNA 和蛋白质表达。通过免疫共沉淀验证 Wnt 型 MMV 整合位点家族成员 5A（WNT5A）和己糖激酶 2（HK2）之间的相互作用。建立异种移植模型以在体内探索 CAFs 对 GC 肿瘤生长的功能。
结果
CAFs 促进了 GC 细胞的增殖、转移、干性和糖酵解。CAFs 中 WNT5A 上调，CAFs 增强了 GC 细胞中的 WNT5A 表达。GC 细胞或 CAFs 中 WNT5A 的敲低抑制了 GC 细胞的进展。此外，WNT5A 促进了 HK2 的表达，而过表达 HK2 逆转了 CAFs 中 WNT5A 敲低对 GC 细胞的影响。此外，CAFs 中 WNT5A 的敲低抑制了体内肿瘤的生长。
结论
CAF 衍生的 WNT5A 通过调节 HK2 表达促进 GC 的进展。
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