Jusino Shirley, Rivera-Rivera Yainyrette, Chardón-Colón Camille, Rodríguez-Rodríguez Patricia C, Román-González Janeishly, Juliá-Hernández Valeria S, Isidro Angel, Mo Qianxing, Saavedra Harold I
Department of Basic Sciences, Ponce Health Sciences University-Ponce Research Institute, 395 Zona Industrial Reparada 2, Ponce, Puerto Rico, 00716-2348, USA.
Department of Biology, University of Puerto Rico-Ponce, 2151 Avenida Santiago de los Caballeros, Ponce, Puerto Rico, 00716, USA.
Cell Div. 2023 Apr 30;18(1):6. doi: 10.1186/s13008-023-00088-5.
Triple-negative breast cancer (TBNC) is an aggressive breast cancer subtype with a poor prognosis. Shugoshin-1 (SGO1) protects chromatids from early separation. Previous studies from our group have demonstrated that transient SGO1 downregulation suppresses early stages of metastasis (the epithelial-to-mesenchymal transition, or EMT, cell invasion, and cell migration) in TNBC cells. Thus, the inhibition of SGO1 activity may represent a potential therapeutic intervention against cancers that progress to metastasis. Therefore, we aimed to investigate the effects of sustained shRNA-mediated SGO1 downregulation on tumor growth and metastasis in TBNC. To that end, female NOD-SCID Gamma (NSG) mice were injected with 2.5 × 10 shRNA Control (n = 10) or shRNA SGO1 (n = 10) MDA-MB-231 cells. After eight weeks, the number of mice with metastasis to the lymph nodes was calculated. Primary and metastatic tumors, as well as lung and liver tissue, were harvested, measured, sectioned, and stained with hematoxylin and eosin (H&E) stain.
Tumor growth and metastasis to the lymph nodes and lungs were significantly reduced in the shRNA SGO1-treated mice group, while metastasis to the liver tends to be lower in cells with downregulated SGO1, but it did not reach statistical significance. Furthermore, sustained SGO1 downregulation significantly reduced cell proliferation, cell migration, and invasion which correlated with lower levels of Snail, Slug, MMP2, MMP3, and MMP9.
The supression of SGO1 activity in TNBC harboring dysregulated expression of SGO1 may be a potential target for preventing breast cancer growth and metastasis.
三阴性乳腺癌（TBNC）是一种侵袭性乳腺癌亚型，预后较差。守护蛋白-1（SGO1）可保护染色单体不提前分离。我们团队之前的研究表明，短暂下调SGO1可抑制三阴性乳腺癌细胞转移的早期阶段（上皮-间质转化，即EMT、细胞侵袭和细胞迁移）。因此，抑制SGO1活性可能是针对进展为转移的癌症的一种潜在治疗干预措施。因此，我们旨在研究持续的shRNA介导的SGO1下调对三阴性乳腺癌肿瘤生长和转移的影响。为此，给雌性NOD-SCID伽马（NSG）小鼠注射2.5×10个shRNA对照（n = 10）或shRNA SGO1（n = 10）MDA-MB-231细胞。八周后，计算发生淋巴结转移的小鼠数量。收集原发肿瘤和转移肿瘤以及肺和肝组织，进行测量、切片，并用苏木精和伊红（H&E）染色。
shRNA SGO1处理的小鼠组的肿瘤生长以及向淋巴结和肺的转移显著减少，而SGO1下调的细胞向肝的转移倾向于较低，但未达到统计学意义。此外，持续下调SGO1可显著降低细胞增殖、细胞迁移和侵袭，这与较低水平 的Snail、Slug、MMP2、MMP3和MMP9相关。
在SGO1表达失调的三阴性乳腺癌中抑制SGO1活性可能是预防乳腺癌生长和转移的潜在靶点。
