RGS10 缺失通过诱导乳腺癌上皮-间充质转化促进远处转移。

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer.

机构信息

Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Elife. 2024 Aug 15;13:RP97327. doi: 10.7554/eLife.97327.

DOI:10.7554/eLife.97327

PMID:39145770

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11326775/

Abstract

Distant metastasis is the major cause of death in patients with breast cancer. Epithelial-mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulates metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and . These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

摘要

远处转移是乳腺癌患者死亡的主要原因。上皮-间充质转化（EMT）促进乳腺癌转移。G 蛋白信号调节蛋白（RGS）蛋白在各种癌症中调节转移。本研究鉴定了 RGS10 在乳腺癌 EMT 和转移中的新作用。与正常乳腺组织相比，RGS10 蛋白水平在乳腺癌组织中显著降低，RGS10 蛋白缺失预测乳腺癌患者预后不良。在高度侵袭性的 MDA-MB-231 细胞系中，RGS10 蛋白水平低于侵袭性较低、侵袭性较弱的 MCF7 和 SKBR3 细胞系。沉默 SKBR3 细胞中的 RGS10 可增强 EMT，并导致 SKBR3 细胞迁移和侵袭。RGS10 抑制乳腺癌 EMT 和转移的能力依赖于脂钙蛋白-2 和。这些发现确定 RGS10 为肿瘤抑制因子、预后生物标志物和乳腺癌潜在的治疗靶点。