PSAT1 通过 p-AKT/SP1/ITGA2 轴促进雌激素受体阴性乳腺癌细胞的转移。

PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell.

机构信息

Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150081, China.

Northern Translational Medical Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin 150081, China.

出版信息

Biomolecules. 2024 Aug 12;14(8):990. doi: 10.3390/biom14080990.

DOI:10.3390/biom14080990

PMID:39199378

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11352415/

Abstract

BACKGROUND

Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits "moonlighting" functions in promoting tumor malignancy. However, the underlying molecular mechanisms of PSAT1 promoting ER-negative breast cancer cell migration need further investigation.

METHODS

Briefly, the PSAT1 and ITGA2 expression in cells and tissues was detected using qRT-PCR, immunofluorescence staining and western blot assay. The effect of PSAT1 and ITGA2 was verified both in vitro and in vivo. RNA-seq analysis explored a series of differently expressed genes. The regulation between SP1 and ITGA2 was investigated by ChIP analysis.

RESULTS

We reported PSAT1 was highly expressed in ER-breast cancer tissues and tumor cells and positively correlated with metastasis. Moreover, RNA-seq analysis explored a series of differently expressed genes, including ITGA2, in PSAT1 overexpressed cells. Mechanistically, PSAT1 facilitated breast cancer metastasis via the p-AKT/SP1/ITGA2 axis. We further elucidated that PSAT1 promoted the entry of SP1 into the nucleus through the upregulation of p-AKT and confirmed ITGA2 is a target of SP1. In addition, enhanced cell migration was remarkably reversed by ITGA2 depletion or p-AKT inhibitor treatment.

CONCLUSION

This study clarified the mechanism of PSAT1 in promoting ER-negative breast cancer metastasis, which may provide mechanistic clues for attenuating breast cancer metastasis.

摘要

背景

越来越多的证据表明 PSAT1 不仅重编程代谢功能，还具有促进肿瘤恶性的“多功能性”。然而，PSAT1 促进 ER-阴性乳腺癌细胞迁移的潜在分子机制仍需进一步研究。

方法

简要地说，使用 qRT-PCR、免疫荧光染色和 Western blot 检测细胞和组织中的 PSAT1 和 ITGA2 表达。在体外和体内验证 PSAT1 和 ITGA2 的作用。RNA-seq 分析探索了一系列差异表达的基因。通过 ChIP 分析研究了 SP1 和 ITGA2 之间的调节关系。

结果

我们报告 PSAT1 在 ER-乳腺癌组织和肿瘤细胞中高表达，并且与转移呈正相关。此外，RNA-seq 分析探索了 PSAT1 过表达细胞中一系列差异表达的基因，包括 ITGA2。从机制上讲，PSAT1 通过 p-AKT/SP1/ITGA2 轴促进乳腺癌转移。我们进一步阐明 PSAT1 通过上调 p-AKT 促进 SP1 进入细胞核，并证实 ITGA2 是 SP1 的靶标。此外，通过 ITGA2 耗竭或 p-AKT 抑制剂处理，显著逆转了增强的细胞迁移。