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TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells
Hee Ju Song1, Young Hwan Kim1, Han Na Choi1
1Department of Physiology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
BMC Molecular and Cell Biology
|March 4, 2024
Summary
Macrophages enhance lung cancer cell survival and migration, increasing resistance to cisplatin. This involves the transcription factor TonEBP/NFAT5, highlighting a new therapeutic target for lung adenocarcinoma.
Area of Science:
- Cancer Biology
- Immunology
- Molecular Oncology
Background:
- Macrophages are known to promote cancer progression, including metastasis and drug resistance.
- The transcription factor TonEBP/NFAT5 is implicated in metastasis in other cancers.
- The specific roles of macrophages and TonEBP/NFAT5 in lung cancer remain largely uncharacterized.
Purpose of the Study:
- To investigate the impact of macrophages on cisplatin resistance and migration in A549 lung adenocarcinoma cells.
- To elucidate the role of TonEBP/NFAT5 in macrophage-mediated drug resistance and metastasis in lung cancer.
Main Methods:
- Indirect co-culture of A549 cells with THP-1 derived macrophages using transwell chambers.
- Treatment of A549 cells with macrophage-conditioned media (CM).
- Assessment of cell death, apoptosis, DNA fragmentation, and protein activity (ERK, p38, JNK, NF-κB).
- Evaluation of TonEBP/NFAT5 expression and its manipulation via RNAi.
- Inhibition studies using specific protein inhibitors.
Main Results:
- Co-culture with macrophages or exposure to macrophage CM significantly decreased cisplatin-induced cell death and increased A549 cell migration.
- Macrophage CM reduced apoptosis and DNA fragmentation, while increasing ERK, p38, JNK, and NF-κB activity.
- TonEBP/NFAT5 expression was upregulated by macrophages, directly contributing to increased cisplatin resistance, migration, and invasion.
Conclusions:
- Paracrine factors from macrophages induce cisplatin resistance and promote migration in A549 lung adenocarcinoma cells.
- Macrophage-induced upregulation of TonEBP/NFAT5 is a key regulator in the malignant transformation of lung cancer cells.
