Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling

Abstract

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.

Dicer-mediated miR-200b expression contributes to cell migratory/invasive abilities and cancer stem cells properties of breast cancer cells

“…For instance, some studies have reported that TBL1XR1 promotes CSCs properties and metastasis in gastric cancer [ 44 ]. In addition, the inhibition of UBQLN1 reduced the invasion and cancer stemness of breast cancer [ 45 ]. Moreover, the inhibition of Dicer expression enhanced the CSCs properties and metastasis in colon cancer cells [ 46 ].…”

Humoral immune response to tumor-associated antigen Ubiquilin 1 (UBQLN1) and its tumor-promoting potential in lung cancer

“…Several previous studies demonstrated that UBQLN1 was involved in crucial biological processes of several cancers [14,[28][29][30][31][32][33], especially epithelial-to-mesenchymal transition (EMT). EMT is a process in which epithelial cells acquire mesenchymal features.…”

“…Hence, it is of importance to understand the relationship between UBQLN1 and EMT pathways in different kinds of cancers. Feng et al discovered that UBQLN1 silencing can inhibit EMT and MMP expression via AKT signaling in breast cancer [33]. Shah et al found that UBQLN1 played an important part in EMT of human non-small cell lung cancer cells and repressed migration [14].…”

Knockdown of UBQLN1 Functions as a Strategy to Inhibit CRC Progression through the ERK-c-Myc Pathway

“…In addition, UBQLN1 is related to the occurrence and progression of a variety of human tumors. UBQLN1 is abnormally upregulated in breast cancer, and the knockdown of UBQLN1 inhibited the invasion and stemness of breast cancer cells through the AKT pathway [ 13 ]. In non-small cell lung carcinoma, loss of UBQLN1 repressed EMT [ 14 ].…”