MPZL1 suppresses the cancer stem-like properties of lung cancer through β-catenin/TCF4 signaling.

Qiao Ge, Chao Zhou, Chao Zang, Chao Li, Haining Hong, Kangwu Wang, Liwei Chen, Haonan Zhu, Ansheng Wang

Functional & integrative genomics 2023 Sep 19

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This study was designed to explore the influence of myelin protein zero-like protein 1 (MPZL1) on the stem-like properties of cancer cells and the underlying mechanism in lung adenocarcinoma. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to evaluate mRNA expression level. CCK8, wound healing, and transwell assays were applied to assess cell proliferation, migration, and invasion. Tumorsphere-formation assay was utilized to assess cancer stem cell-like properties. LF3 was used to block the β-catenin/Transcription factor 4 (TCF-4) signaling. Xenograft nude mouse model was conducted; tumor weight and volume were recorded. Western blot assay was utilized to detect the expression levels of CD44, CD133, β-catenin, TCF-4, and MPZL1. Following MPZL1 knockdown, the mRNA expression levels of MPZL1, β-catenin, and TCF-4 were inhibited, while the mRNA expression levels of the above genes were increased after the MPZL1 overexpression. MPZL1 knockdown suppressed cell proliferation, migration, and invasion, reduced the tumorsphere-formation capacity, and restrained the expression levels of CD44 and CD133. However, MPZL1 overexpression promoted the cell proliferation, migration, and invasion, enhanced the tumorsphere-formation capacity, and increased the expression levels of CD44 and CD133. Interestingly, LF3 treatment partially revised the effect of MPZL1 overexpression. These findings were further corroborated by in vivo experiments. We concluded that MPZL1 could suppress the lung adenocarcinoma cells' proliferation, migration, invasion, and lung cancer stem cells characteristics. The underlying mechanism is involved in the activation of β-catenin/TCF-4 signaling. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Qiao Ge, Chao Zhou, Chao Zang, Chao Li, Haining Hong, Kangwu Wang, Liwei Chen, Haonan Zhu, Ansheng Wang. MPZL1 suppresses the cancer stem-like properties of lung cancer through β-catenin/TCF4 signaling. Functional & integrative genomics. 2023 Sep 19;23(4):304