Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int J Biol Sci. 2023 Jul 24;19(12):3816-3829. doi: 10.7150/ijbs.83134. eCollection 2023.
Cancer cells inevitably develop radioresistance during lung adenocarcinoma radiotherapy. However, the mechanisms are incompletely clarified. In this study, we show that FIBP protein expression in lung adenocarcinoma tissues is upregulated and associated with worse overall survival. Functionally, we find that depletion of FIBP inhibits lung adenocarcinoma progression and radioresistance and . Moreover, we uncover that FIBP interacts with STAT3 to enhance its transcriptional activity, thereby inducing the expression of the downstream target gene EME1. Importantly, we demonstrate that the biological effects of FIBP are partially dependent on EME1 in lung adenocarcinoma. Our work reveals that FIBP modulates the STAT3/EME1 axis to drive lung cancer progression and radioresistance, indicating that targeting FIBP may be a novel intervention strategy for lung adenocarcinoma radiotherapy.
在肺腺癌放疗过程中，癌细胞不可避免地会产生放射抗性。然而，其机制尚不完全清楚。在本研究中，我们发现 FIBP 蛋白在肺腺癌组织中的表达上调，并与总生存期不良相关。功能上，我们发现 FIBP 的缺失可抑制肺腺癌的进展和放射抗性。此外，我们发现 FIBP 与 STAT3 相互作用以增强其转录活性，从而诱导下游靶基因 EME1 的表达。重要的是，我们证明 FIBP 在肺腺癌中的部分生物学效应依赖于 EME1。我们的工作揭示了 FIBP 调节 STAT3/EME1 轴以驱动肺癌的进展和放射抗性，表明靶向 FIBP 可能是肺腺癌放疗的一种新的干预策略。
