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CD40 连接诱导的 ERK 激活通过促进自噬导致宫颈癌细胞放射敏感性增强。

CD40 ligation-induced ERK activation leads to enhanced radiosensitivity in cervical carcinoma cells via promoting autophagy.

作者信息

Liu Baocai, Zhang Yadong, Wang Quan, Wang Qian, Wang Zhixin, Feng Li

机构信息

Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

Department of Urology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2024 Dec 17;57(8):1252-1259. doi: 10.3724/abbs.2024229.

Abstract

CD40, a member of the tumor necrosis factor (TNF) receptor superfamily, plays an important role not only in the immune system but also in tumor progression. CD40 ligation reportedly promotes autophagy in immune cells. However, the effects of CD40 ligation on autophagy and its mechanism in solid tumor cells are still unclear. In this study, we find that CD40 ligation promotes autophagosome formation and consequently promotes autophagic flux in cervical cancer cells. Mechanistically, this effect relies on ERK contributing to CD40 ligation-induced ATG13 upregulation by p53. Furthermore, we demonstrate that CD40 ligation-induced autophagy increases the radiosensitivity of cervical cancer cells. Taken together, our results provide new evidence for the involvement of the CD40 pathway in autophagy and radiotherapy in cervical cancer cells.

摘要

CD40是肿瘤坏死因子(TNF)受体超家族的成员,不仅在免疫系统中发挥重要作用,还在肿瘤进展中起作用。据报道,CD40连接可促进免疫细胞中的自噬。然而,CD40连接对实体瘤细胞自噬的影响及其机制仍不清楚。在本研究中,我们发现CD40连接促进自噬体形成,从而促进宫颈癌细胞中的自噬流。机制上,这种作用依赖于ERK通过p53促进CD40连接诱导的ATG13上调。此外,我们证明CD40连接诱导的自噬增加了宫颈癌细胞的放射敏感性。综上所述,我们的结果为CD40通路参与宫颈癌细胞的自噬和放疗提供了新证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f62c/12368552/55a4111e2558/t1.jpg

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