ASS1 的 PGAM1 调节通过 cAMP/AMPK/CEBPB 通路促进乳腺癌的进展,Molecular Oncology

当前位置： X-MOL 学术 › Mol. Oncol. › 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.)

ASS1 的 PGAM1 调节通过 cAMP/AMPK/CEBPB 通路促进乳腺癌的进展
Molecular Oncology ( IF 5.0 ) Pub Date : 2022-06-08 , DOI: 10.1002/1878-0261.13259
Min Liu ₁ , Runmei Li ₁ , Min Wang ₁ , Ting Liu ₁ , Qiuru Zhou ₁ , Dong Zhang ₁ , Jian Wang ₁ , Meng Shen ₁ , Xiubao Ren ₁ , Qian Sun ₁

Affiliation

磷酸甘油酸变位酶 1 ( PGAM1 ) 是一种重要的糖酵解酶，其表达状态已被证实与肿瘤进展和转移有关。然而，PGAM1的确切作用和其他生物学功能仍不清楚。在这里，我们报告PGAM1表达上调并与乳腺癌 (BC) 患者的不良预后有关。功能实验表明，敲低PGAM1可以抑制 BC 细胞的增殖、侵袭、迁移和上皮-间质转化。通过 RNA 测序，我们发现精氨琥珀酸合酶 1 ( ASS1 ) 的表达在PGAM1后在 BC 细胞中显着上调敲低，并且需要抑制BC细胞的恶性生物学行为。重要的是，我们证明PGAM1通过cAMP/AMPK/CEBPB轴负向调节ASS1的表达。体内实验进一步验证了PGAM1通过改变ASS1的表达促进了 BC 中的肿瘤生长。最后，免疫组化分析显示，下调的 ASS1 水平与 BC 患者的PGAM1表达和不良预后相关。我们的研究为PGAM1的调控机制提供了新的见解-介导的 BC 进展可能为 BC 治疗的潜在靶点和联合治疗策略提供新的启示。

"点击查看英文标题和摘要"

PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway

Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis. However, the precise role and other biological functions of PGAM1 remain unclear. Here, we report that PGAM1 expression is upregulated and related to poor prognosis in patients with breast cancer (BC). Functional experiments showed that knockdown of PGAM1 could suppress the proliferation, invasion, migration, and epithelial–mesenchymal transition of BC cells. Through RNA sequencing, we found that argininosuccinate synthase 1 (ASS1) expression was markedly upregulated in BC cells following PGAM1 knockdown, and it is required to suppress the malignant biological behavior of BC cells. Importantly, we demonstrated that PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB axis. In vivo experiments further validated that PGAM1 promoted tumor growth in BC by altering ASS1 expression. Finally, immunohistochemical analysis showed that downregulated ASS1 levels were associated with PGAM1 expression and poor prognosis in patients with BC. Our study provides new insight into the regulatory mechanism of PGAM1-mediated BC progression that might shed new light on potential targets and combination therapeutic strategies for BC treatment.

更新日期：2022-06-08

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