SLC4A7 suppresses lung adenocarcinoma oncogenesis by reducing lactate transport and protein lactylation
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- Published online on: March 14, 2025 https://doi.org/10.3892/ijo.2025.5739
- Article Number: 33
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Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
Lactate and protein lactylation serve a key role in tumor pathogenesis. Solute carrier 4A7 (SLC4A7), a key transporter, participates in cellular acid homeostasis. However, its impact on lactate transport and protein lactylation in solid tumors, particularly lung adenocarcinoma (LUAD), remains largely unexplored. In the present study, lactylome analysis, Transwell and wound healing assay, animal experiments were conducted to validate functional regulation mediated by SLC4A7 in LUAD. SLC4A7 inhibited tumor progression, including metastasis, invasion and proliferation. Mechanistically, SLC4A7 decreased both intracellular and extracellular lactate accumulation and inhibited overall protein lactylation, as confirmed by lactylome analysis. Analyzing the lactylome revealed that SLC4A7 suppressed lysine lactylation of numerous genes like HSP90AA1 and pathways such as focal adhesion associated with carcinogenesis. Additionally, low expression levels of SLC4A7 in LUAD cancer stem cells were validated using tumor tissue samples from patients with LUAD. Moreover, the inhibitory role of SLC4A7 in regulating tumor stemness was verified. Collectively, the present results uncovered the inhibitory effect exerted by SLC4A7 on tumor progression via its regulation of lactate transport, protein lactylation and stemness properties. Targeting SLC4A7 may hold promise as a novel therapeutic strategy for LUAD.
