Ubiquilin‑1 (UBQLN1) is an essential factor for the maintenance of proteostasis in cells. It is important for the regulation of different protein degradation mechanisms, including the ubiquitin‑proteasome system, autophagy and endoplasmic reticulum‑associated protein degradation pathways. However, the role of UBQLN1 in cancer progression remains largely unknown. In the present study, the expression, functions and molecular mechanisms of UBQLN1 in breast cancer tissue samples and cell lines were explored. Immunohistochemical and bioinformatics analyses revealed that UBQLN1 expression was significantly upregulated in breast cancer tissues and cell lines. UBQLN1 expression in breast cancer was significantly associated with lymph node metastasis and TNM stage. Moreover, a high UBQLN1 expression was a predictor of an unfavorable survival in patients with breast cancer. In vitro, UBQLN1 silencing markedly inhibited cell migration and invasion, epithelial‑to‑mesenchymal transition (EMT) and MMP expression. UBQLN1 silencing attenuated the stem cell‑like properties of breast cancer cells, including their mammosphere‑forming abilities. UBQLN1 knockdown also enhanced breast cancer cell chemosensitivity to paclitaxel. The expression levels of the stem cell markers. Aldehyde dehydrogenase 1 (ALDH1), Oct‑4 and Sox2 were significantly decreased in the cells in which UBQLN1 was silenced, whereas breast cancer stem cells exhibited an increased expression of UBQLN1. Mechanistically, UBQLN1 knockdown inhibited the activation of AKT signaling, as revealed by the increased PTEN expression and the decreased expression of phosphorylated AKT in cells in which UBQLN1 was silenced. On the whole, the present study demonstrates that UBQLN1 is aberrantly upregulated in breast cancer and predicts a poor prognosis. The silencing of UBQLN1 inhibited the invasion, EMT and stemness of breast cancer cells, possibly via AKT signaling.

中文翻译：

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乳腺癌中异常升高的泛素-1 表达通过 AKT 信号调节转移和干性。

Ubiquilin-1 (UBQLN1) 是维持细胞内蛋白质稳态的重要因素。它对于调节不同的蛋白质降解机制很重要，包括泛素-蛋白酶体系统、自噬和内质网相关的蛋白质降解途径。然而，UBQLN1 在癌症进展中的作用仍然未知。本研究探索了UBQLN1在乳腺癌组织样本和细胞系中的表达、功能和分子机制。免疫组织化学和生物信息学分析表明，UBQLN1 表达在乳腺癌组织和细胞系中显着上调。UBQLN1在乳腺癌中的表达与淋巴结转移和TNM分期显着相关。而且，体外, UBQLN1 沉默显着抑制细胞迁移和侵袭、上皮间质转化 (EMT) 和 MMP 表达。UBQLN1 沉默减弱了乳腺癌细胞的干细胞样特性，包括它们的乳腺球形成能力。UBQLN1 敲低还增强了乳腺癌细胞对紫杉醇的化学敏感性。干细胞标志物的表达水平。在 UBQLN1 沉默的细胞中，醛脱氢酶 1 (ALDH1)、Oct-4 和 Sox2 显着降低，而乳​​腺癌干细胞的 UBQLN1 表达增加。从机制上讲，UBQLN1 敲低抑制了 AKT 信号的激活，正如在 UBQLN1 沉默的细胞中 PTEN 表达增加和磷酸化 AKT 表达降低所揭示的那样。总体上，本研究表明 UBQLN1 在乳腺癌中异常上调，并预示着预后不良。UBQLN1 的沉默抑制了乳腺癌细胞的侵袭、EMT 和干性，可能是通过 AKT 信号传导。