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KLK11 acts as a tumor-inhibitor in laryngeal squamous cell carcinoma through the inactivation of Akt/Wnt/β-catenin signaling

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Abstract

Kallikrein-associated peptidase 11 (KLK11) has emerged as a key tumor-associated protein that is implicated in a wide spectrum of tumor types. However, the detailed involvement of KLK11 in laryngeal squamous cell carcinoma (LSCC) has not been well studied. The aims of our work were to evaluate whether KLK11 plays a role in LSCC. We found that both the mRNA and protein expression of KLK11 were significantly lower in LSCC tissues than in normal tissues. Low expression of KLK11 was also observed in LSCC cell lines, and the up-regulation of KLK11 caused a significant inhibitory effect on the proliferation, colony formation and invasion of LSCC cells. On the contrary, the knockdown of KLK11 markedly accelerated the proliferative and invasive abilities of LSCC cells. Molecular mechanism research revealed that KLK11 overexpression decreased the phosphorylation of glycogen synthase kinase-3β (GSK-3β) and down-regulated the expression of active β-catenin, leading to the inactivation of Wnt/β-catenin signaling in LSCC cells. Furthermore, GSK-3β inhibition markedly abrogated the KLK11-mediated suppressive effect on Wnt/β-catenin signaling. Notably, the reactivation of Wnt/β-catenin partially reversed KLK11-mediated tumor-inhibition effect in LSCC. In addition, the xenograft tumor assay demonstrated that the up-regulation of KLK11 retarded tumor formation and the growth of LSCC cells in vivo. Taken together, the findings of our work demonstrate that KLK11 exerts a tumor-inhibition role in LSCC by down-regulating Wnt/β-catenin signaling. Our work highlights a pivotal role of KLK11 in LSCC progression and suggests it as an attractive anticancer target for LSCC treatment.

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The data and material used to support the findings of this study are available from the corresponding author upon request.

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Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province, China

    Ruimin Zhao, Shiyang Wang, Junsong Liu, Chongwen Xu, Shaoqiang Zhang & Yuan Shao

  2. Department of Medical Image and Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, No.277 Yanta West Road, Xi’an, 710061, Shaanxi Province, China

    Xiaoyi Duan

Authors
  1. Ruimin Zhao
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  2. Shiyang Wang
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  3. Junsong Liu
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  4. Chongwen Xu
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  5. Shaoqiang Zhang
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  6. Yuan Shao
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  7. Xiaoyi Duan
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Contributions

Ruimin Zhao designed the study, performed the experiments and drafted the manuscript. Shiyang Wang performed the experiments. Junsong Liu performed the experiments. Chongwen Xu collected and analyzed the data. Shaoqiang Zhang collected and analyzed the data. Yan Shao collected and analyzed the data. Xiaoyi Duan designed the study and revised the manuscript.

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Correspondence to Xiaoyi Duan.

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The authors declare that they have no conflict of interest.

Ethics approval

The use of clinical specimens was approved by the Ethics Committee of Xi’an Jiaotong University, and experiments were managed in accordance with the ordinances of the Declaration of Helsinki. Animal care and experimental procedures complied with the guidelines of the Ethics Committee of Xi’an Jiaotong University.

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Written informed consent for tissue donation for scientific study were acquired from all patients.

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Zhao, R., Wang, S., Liu, J. et al. KLK11 acts as a tumor-inhibitor in laryngeal squamous cell carcinoma through the inactivation of Akt/Wnt/β-catenin signaling. J Bioenerg Biomembr 53, 85–96 (2021). https://doi.org/10.1007/s10863-020-09870-4

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  • DOI: https://doi.org/10.1007/s10863-020-09870-4

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