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 RGS10 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 MIR539-5p. 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-间质转化(EMT)有助于乳腺癌的转移。G蛋白信号调节因子(RGS)蛋白调节各种癌症的转移。这项研究确定了RGS10在乳腺癌EMT和转移中的新作用。RGS10蛋白水平在乳腺癌组织中显著低于正常乳腺组织,RGS10蛋白的缺乏预示着乳腺癌患者的预后较差。高侵袭性细胞系MDA-MB-231中的RGS10蛋白水平低于低侵袭性细胞系MDA-MB-231,侵袭性较小的细胞系MCF7和SKBR3。在SKBR3细胞中沉默RGS10可增强EMT并引起SKBR3细胞迁移和侵袭。RGS10抑制乳腺癌EMT和转移的能力取决于脂质运载蛋白2和MIR539-5p。这些发现将RGS10确定为肿瘤抑制因子,预后生物标志物,和潜在的乳腺癌治疗靶点。