Scientific Reports (Jan 2024)

Protein interaction networks characterizing the A549 cells Klotho transfected are associated with activated pro-apoptotic Bim and suppressed Wnt/β-catenin signaling pathway

  • Mitsuo Matsumoto,
  • Naomi Ogawa,
  • Tetsuya Fukuda,
  • Yasuhiko Bando,
  • Toshihide Nishimura,
  • Jitsuo Usuda

DOI
https://doi.org/10.1038/s41598-024-52616-0
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 18

Abstract

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Abstract Invasive assays and lung tumor-bearing mice models using a human lung adenocarcinoma cell line A549 cells transfected with the Klotho (KL) gene, A549/KL cells, have confirmed that KL suppresses invasive/metastatic potential. This study aimed to identify the co-expression protein networks and proteomic profiles associated with A549/KL cells to understand how Klotho protein expression affects molecular networks associated with lung carcinoma malignancy. A two-step application of a weighted network correlation analysis to the cells’ quantitative proteome datasets of a total of 6,994 proteins, identified by mass spectrometry-based proteomic analysis with data-independent acquisition (DIA), identified one network module as most significantly associated with the A549/KL trait. Upstream analyses, confirmed by western blot, implicated the pro-apoptotic Bim (Bcl-2-like protein 11) as a master regulator of molecular networks affected by Klotho. GeneMANIA interaction networks and quantitative proteome data implicated that Klotho interacts with two signaling axes: negatively with the Wnt/β-catenin axis, and positively by activating Bim. Our findings might contribute to the development of future therapeutic strategies.