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Spindle and kinetochore‑associated complex subunit 3 accelerates breast cancer cell proliferation and invasion through the regulation of Akt/Wnt/β-catenin signaling

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Abstract

Purpose

Spindle and kinetochore‑associated complex subunit 3 (SKA3) has recently been identified as a novel regulator of carcinogenesis in multiple types of cancers. However, the function and potential regulatory mechanisms of SKA3 in breast cancer remain poorly understood. The present study was designed to gain a detailed relevance of SKA3 in breast cancer.

Methods

Expression of SKA3 in breast cancer was examined via real-time quantitative PCR, western blotting and immunohistochemistry analysis. Malignant behaviors of breast cancer cells were investigated via cell counting kit-8, cell apoptosis, and transwell invasion assays. The activity of Wnt/β-catenin signaling was monitored via luciferase reporter assay. The tumorigenicity of breast cancer cells in vivo was assessed via xenograft tumor assay.

Results

SKA3 expression was elevated in breast cancer tissue and was correlated with shorter survival rates in breast cancer patients. Knockdown of SKA3 caused marked reductions in cellular proliferation and invasion in breast cancer cells, whereas SKA3 overexpression accelerated proliferation and invasion. Knockdown of SKA3 resulted in decreased Akt and glycogen synthase kinase-3β phosphorylation, and decreased expression of active β-catenin, which lead to the inactivation of Wnt/β-catenin signaling. Inhibition of Akt significantly reversed the SKA3 overexpression-induced activation of Wnt/β-catenin signaling. Inhibition of Wnt/β-catenin signaling markedly abrogated SKA3 overexpression-induced tumor-promotion effects, while re-activation of Wnt/β-catenin signaling significantly reversed SKA3 knockdown-mediated tumor-inhibition effects. Knockdown of SKA3 resulted in a significant decrease in breast cancer tumor formation in vivo.

Conclusions

SKA3 accelerates proliferation and invasion in breast cancer through the modulation of Akt/Wnt/β-catenin signaling.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta Western Road, Xi’an, 710061, Shaanxi, China

    Jian Zhang, Yang Liu, Shengyu Pu, Jianjun He & Can Zhou

Authors
  1. Jian Zhang
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  2. Yang Liu
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  3. Shengyu Pu
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  4. Jianjun He
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  5. Can Zhou
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Corresponding authors

Correspondence to Jianjun He or Can Zhou.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

Ethical approval to report this case was obtained from the Ethics Committee of Xi’an Jiaotong University. Experimental protocols were performed in compliance with the guidelines of Declaration of Helsinki. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study. Written informed consent forms were acquired from all participants before surgery and collection of materials. All authors have approved for the publication of the data of this manuscript.

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Zhang, J., Liu, Y., Pu, S. et al. Spindle and kinetochore‑associated complex subunit 3 accelerates breast cancer cell proliferation and invasion through the regulation of Akt/Wnt/β-catenin signaling. Breast Cancer Res Treat 186, 247–258 (2021). https://doi.org/10.1007/s10549-020-06078-3

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  • DOI: https://doi.org/10.1007/s10549-020-06078-3

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