RON receptor tyrosine kinase regulates glycolysis through MAPK/CREB signaling to affect ferroptosis and chemotherapy sensitivity of thyroid cancer cells

Jin,Xin; Zhu,Haonan; Chen,Xingyu; Yang,Yining; Song,Dongliang

doi:10.3892/mmr.2024.13359

RON receptor tyrosine kinase regulates glycolysis through MAPK/CREB signaling to affect ferroptosis and chemotherapy sensitivity of thyroid cancer cells

Authors:
- Xin Jin
- Haonan Zhu
- Xingyu Chen
- Yining Yang
- Dongliang Song
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Affiliations: School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China
Published online on: October 14, 2024 https://doi.org/10.3892/mmr.2024.13359
Article Number: 234
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anaplastic thyroid cancer (ATC) is one of the deadliest and most aggressive human malignancies for which there is currently no effective treatment. Tyrosine kinase receptor RON is highly expressed in various cancer types, including colon, pancreatic and thyroid cancer. However, its underlying role in ATC is not fully understood. The present study investigated the therapeutic potential and molecular mechanism of RON in ATC. RON expression in thyroid cancer cells was detected by western blotting. Glycolysis was assessed by measuring the extracellular acidification rate, glucose uptake, lactate concentration, and expression levels of glucose transporter 1, hexokinase 2 and pyruvate kinase M1/2. In addition, ferroptosis was assessed by detecting the levels of total iron, lipid peroxide and reactive oxygen species, and the expression levels of ferroptosis‑related proteins. Furthermore, mitochondrial function were assessed by JC‑1 staining and detection kits, respectively. The results demonstrated that RON was highly expressed in thyroid cancer cell lines. Furthermore, RON interference inhibited glycolysis, promoted ferroptosis, elevated cell sensitivity to chemotherapy and affected mitochondrial function in thyroid cancer cells. Further experiments demonstrated that RON interference affected the ferroptosis levels in thyroid cancer cells by inhibiting the glycolysis process. Mechanistically, the present results indicated that RON may affect ferroptosis, glycolysis and chemotherapy sensitivity by regulating MAPK/cAMP‑response element binding protein (CREB) signaling in thyroid cancer cells. In conclusion, the present study demonstrated that RON affected ferroptosis, glycolysis and chemotherapy sensitivity in thyroid cancer cells by regulating MAPK/CREB signaling, demonstrating its potential as a therapeutic target in thyroid cancer cells.

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