Open Access

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

  • Authors:
    • Xiaoyue Feng
    • Anna Cao
    • Tao Qin
    • Qingqing Zhang
    • Shujun Fan
    • Bo Wang
    • Bo Song
    • Xiaotang Yu
    • Lianhong Li
  • View Affiliations

  • Published online on: September 15, 2021     https://doi.org/10.3892/or.2021.8187
  • Article Number: 236
  • Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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November-2021
Volume 46 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Feng X, Cao A, Qin T, Zhang Q, Fan S, Wang B, Song B, Yu X and Li L: Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling. Oncol Rep 46: 236, 2021
APA
Feng, X., Cao, A., Qin, T., Zhang, Q., Fan, S., Wang, B. ... Li, L. (2021). Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling. Oncology Reports, 46, 236. https://doi.org/10.3892/or.2021.8187
MLA
Feng, X., Cao, A., Qin, T., Zhang, Q., Fan, S., Wang, B., Song, B., Yu, X., Li, L."Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling". Oncology Reports 46.5 (2021): 236.
Chicago
Feng, X., Cao, A., Qin, T., Zhang, Q., Fan, S., Wang, B., Song, B., Yu, X., Li, L."Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling". Oncology Reports 46, no. 5 (2021): 236. https://doi.org/10.3892/or.2021.8187