Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, Liaoning Province, China.
Ann N Y Acad Sci. 2019 Jul;1448(1):5-18. doi: 10.1111/nyas.14039. Epub 2019 Mar 22.
Endothelin receptor B (EDNRB) is one of the receptors in the endothelin axis and its upregulated expression is associated with tumorigenesis and metastasis of several types of solid tumors. However, the expression profile of EDNRB in breast cancer and its role in the progression of breast cancer are unclear. Here, we show that EDNRB expression is higher in metastatic tumors than in primary breast cancer, and is associated significantly with lymph node metastasis and poor survival in Chinese patients with breast cancer. EDNRB expression was particularly upregulated in triple-negative breast cancer (TNBC) cells. Moreover, EDNRB silencing by a specific shRNA significantly attenuated the proliferation, migration, and invasiveness of MDA-MB-231 and BT549 cells and increased their apoptosis, as well as retarded the growth of implanted tumors in mice. Tandem mass spectrometry analysis indicated that 248 proteins were differentially expressed in EDNRB-silenced cells and their cellular organelles, and these proteins participate in many processes. EDNRB silencing decreased protein kinase B and extracellular regulated protein kinase phosphorylation and promoted the mesenchymal-to-epithelial transition process in MDA-MB-231 cells. Therefore, our findings provide strong evidence for the first time that knockdown of EDNRB expression inhibits the progression of TNBC and that EDNRB can serve as a prognostic biomarker and therapeutic target for the treatment of TNBC.
内皮素受体 B（EDNRB）是内皮素轴中的一种受体，其表达上调与多种实体瘤的发生和转移有关。然而，EDNRB 在乳腺癌中的表达谱及其在乳腺癌进展中的作用尚不清楚。在这里，我们表明 EDNRB 表达在转移性肿瘤中高于原发性乳腺癌，并且与中国乳腺癌患者的淋巴结转移和不良预后显著相关。EDNRB 表达在三阴性乳腺癌（TNBC）细胞中特别上调。此外，特异性 shRNA 沉默 EDNRB 显著减弱了 MDA-MB-231 和 BT549 细胞的增殖、迁移和侵袭能力，并增加了它们的凋亡，同时延缓了小鼠植入肿瘤的生长。串联质谱分析表明，EDNRB 沉默细胞及其细胞细胞器中有 248 种蛋白质表达差异，这些蛋白质参与许多过程。EDNRB 沉默降低了蛋白激酶 B 和细胞外调节蛋白激酶的磷酸化，并促进了 MDA-MB-231 细胞中的间质到上皮转化过程。因此，我们的研究结果首次提供了强有力的证据，表明 EDNRB 表达的敲低抑制了 TNBC 的进展，并且 EDNRB 可以作为 TNBC 治疗的预后生物标志物和治疗靶点。
