School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China.
Mol Med Rep. 2024 Dec;30(6). doi: 10.3892/mmr.2024.13359. Epub 2024 Oct 18.
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.
间变性甲状腺癌（ATC）是目前尚无有效治疗方法的最致命和最具侵袭性的人类恶性肿瘤之一。酪氨酸激酶受体 RON 在多种癌症类型中高度表达，包括结肠癌、胰腺癌和甲状腺癌。然而，其在 ATC 中的潜在作用尚未完全阐明。本研究探讨了 RON 在 ATC 中的治疗潜力和分子机制。通过 Western blot 检测甲状腺癌细胞中 RON 的表达。通过测量细胞外酸化率、葡萄糖摄取、乳酸浓度以及葡萄糖转运蛋白 1、己糖激酶 2 和丙酮酸激酶 M1/2 的表达水平来评估糖酵解。此外，通过检测总铁、脂质过氧化物和活性氧水平以及铁死亡相关蛋白的表达水平来评估铁死亡。此外，通过 JC-1 染色和检测试剂盒分别评估线粒体功能。结果表明，RON 在甲状腺癌细胞系中高度表达。此外，RON 干扰抑制糖酵解，促进铁死亡，提高甲状腺癌细胞对化疗的敏感性，并影响线粒体功能。进一步的实验表明，RON 干扰通过抑制糖酵解过程影响甲状腺癌细胞的铁死亡水平。机制上，本研究结果表明，RON 通过调节甲状腺癌细胞中的 MAPK/cAMP 反应元件结合蛋白（CREB）信号通路影响铁死亡、糖酵解和化疗敏感性。综上所述，本研究表明，RON 通过调节 MAPK/CREB 信号通路影响甲状腺癌细胞中的铁死亡、糖酵解和化疗敏感性，表明其在甲状腺癌细胞中具有作为治疗靶点的潜力。
