Protein Interaction Networks Characterizing the A549 Cells Klotho Transfected Are Associated with Activated Pro-apoptotic Bim and Suppressed Wnt/β-catenin Signaling Pathway

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jan 24

PMID 38267588

Authors

Mitsuo Matsumoto

Naomi Ogawa

Tetsuya Fukuda

Yasuhiko Bando

Toshihide Nishimura

Jitsuo Usuda

Affiliations

Soon will be listed here.

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.

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