Radiation and Cancer Biology

PD 07 - Biology 3 - Poster Discussion

1062 - CD40 Ligation-Induced Autophagy by Increasing ATG13 Expression Suppresses its Promoted Radiosensitivity in Cervical Carcinoma Cells

Monday, October 22
4:57 PM - 5:03 PM
Location: Room 217 C/D

CD40 Ligation-Induced Autophagy by Increasing ATG13 Expression Suppresses its Promoted Radiosensitivity in Cervical Carcinoma Cells
G. Cheng1, B. Liu2, D. Han3, and T. Zhang2; 1China-Japan Union Hospital of Jilin University, Changchun, China, 2Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun, China, 3China-Japan Union Hospital of Jilin University, Changchun, China, Changchun, China

Purpose/Objective(s): Radiotherapy is one of the main means of radical treatment for cervical carcinoma, but the local control and prognosis of patients with cervical carcinoma remains poor. Accumulating evidence suggests that autophagy is involved in the radiosensitivity of cervical carcinoma and its progression. The current study has demonstrated that CD40 ligation promotes autophagy in immune cells. However, the effects of CD40 ligation on autophagy in solid tumors and the radiosensitivity of cervical carcinoma are still unclear. This study aimed to elucidate whether CD40 ligation affects autophagy and its underlying mechanisms, as well as its relationship with radiosensitivity in cervical carcinoma cells.

Materials/Methods: Western blot was used to detect the levels of proteins involved in CD40 signaling and autophagy. The localization of autophagy-related molecules was observed by confocal microscopy. CCK8 and colony formation assay were performed to assess the radiosensitivity.

Results: In this study, we found that CD40 ligation promoted autophagic flux in HeLa cells stably overexpressing CD40, as evidenced by elevated levels of markers present in stages of autophagosome biogenesis, such as ZFYVE1-labeled vesicles, autophagy-related protein (ATG)5-labeled membrane structures, and LC3B-II, and increased fusion of autophagosomes with lysosomes and accumulated free GFP released from the GFP-LC3B protein by autolysosome degradation. Knockdown of CD40 impaired CD40 ligation-mediated autophagy in SiHa cells. Additionally, CD40 ligation was observed to increase ATG13 expression to stabilize ULK1 and increase the interaction of ATG13 and ULK1. Importantly, extracellular signal-regulated kinase contributed to CD40 ligation-induced ATG13 upregulation, leading to enhanced autophagy. We then found that CD40 ligation enhanced the radiation-induced LC3B-II accumulation and the radiosensitivity of cervical carcinoma cells. Furthermore, the autophagy/lysosome inhibitor chloroquine further promoted CD40 ligation-mediated hypersensitivity to radiotherapy.

Conclusion: CD40 ligation-induced ERK activation promotes autophagy by increasing ATG13 expression in cervical carcinoma cells. CD40 ligation-induced autophagy transduces survival signaling capable of suppressing its effect on radiosensitivity. Taken together, our results first provide evidence for involvement of the CD40 pathway in autophagy and radiosensitisity in cervical carcinoma cells.

Author Disclosure: G. Cheng: None. B. Liu: None.

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