Department of Breast and Thyroid Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107 ShenZhen, Guangdong, China.
Department of Microbiology, School of Public Health, Southern Medical University, 510515 Guangzhou, Guangdong, China.
Front Biosci (Landmark Ed). 2024 Oct 30;29(11):371. doi: 10.31083/j.fbl2911371.
Breast cancer is the most common malignancy and the leading cause of cancer death among women. NDC80 kinetochore complex component (NUF2) is demonstrated to implicate the progression of human cancer. But the role of NUF2 in breast cancer progression is unclear. Here, we aimed to study the role and regulatory mechanisms of NUF2 in breast cancer metastasis.
Immunohistochemistry was used to determine UNF2 expression in clinical samples. Transwell assas were used to determine the role of NUF2 in breast cancer migration and invasion. Animal model was used to determine the rold of NUF2 in breast cancer metastasis.
NUF2 was upregulated significantly in breast cancer tissues and cells. Worse prognosis was noted in patients with high NUF2 levels compared with that in patients with low NUF2 levels. NUF2 overexpression markedly enhanced, while NUF2 knockdown inhibited, breast cancer cell invasion and migration. Mechanistically, NUF2 was observed to upregulate Wnt/β-catenin signaling pathway activity. The promoting effect of NUF2 on cell migration and invasion were blocked by inhibition of the Wnt/β-catenin pathway.
We revealed that NUF2 promotes breast cancer progression via activating Wnt/β-catenin signaling, suggesting that NUF2 might be a new potential target for breast cancer treatment.
乳腺癌是最常见的恶性肿瘤,也是女性癌症死亡的主要原因。NDC80 着丝粒复合物成分(NUF2)被证明与人类癌症的进展有关。但 NUF2 在乳腺癌进展中的作用尚不清楚。在这里,我们旨在研究 NUF2 在乳腺癌转移中的作用和调节机制。
免疫组织化学法用于检测临床样本中 UNF2 的表达。Transwell 分析用于确定 NUF2 在乳腺癌迁移和侵袭中的作用。动物模型用于确定 NUF2 在乳腺癌转移中的作用。
NUF2 在乳腺癌组织和细胞中显著上调。与 NUF2 水平低的患者相比,NUF2 水平高的患者预后更差。NUF2 过表达显著增强,而 NUF2 敲低则抑制乳腺癌细胞的侵袭和迁移。机制上,观察到 NUF2 上调 Wnt/β-catenin 信号通路活性。Wnt/β-catenin 通路的抑制阻断了 NUF2 对细胞迁移和侵袭的促进作用。
我们揭示了 NUF2 通过激活 Wnt/β-catenin 信号促进乳腺癌进展,表明 NUF2 可能成为乳腺癌治疗的新潜在靶点。