SorCS3 suppresses adrenocortical carcinoma progression by enhancing IGF2R-mediated endocytic trafficking and signaling attenuation
In this study, we identified SorCS3 as a novel tumor suppressor candidate in ACC. Although previously thought to be CNS specific, SorCS3 was found to be expressed in ACC tissues and cell lines. Low SorCS3 levels correlated with poor patient survival in the TCGA cohort. Functionally, SorCS3 enhanced endocytosis in ACC cells and physically or indirectly interacted with IGF2R. OE-SorCS3 increased IGF2R protein levels and reduced phosphorylation of Akt/Erk, suggesting tumor-suppressive effects through IGF2R stabilization and signaling inhibition. Overall, our findings highlight the SorCS3-IGF2R axis as a previously unrecognized regulatory mechanism in ACC progression and suggest that receptor trafficking could be a viable therapeutic target in this malignancy.
Authors
- Feifei Zheng (ORCID: https://orcid.org/0000-0003-3048-7086)
- Jin‐Lai Gao (ORCID: https://orcid.org/0009-0004-0106-1451)
- Dongliang Li (ORCID: https://orcid.org/0000-0003-2026-0769)
- Yuchen Zhao (ORCID: https://orcid.org/0009-0007-1097-9063)
- Zhang Shi (ORCID: https://orcid.org/0000-0001-7739-7497)
- Haiyan Xu (ORCID: https://orcid.org/0000-0001-7420-7715)
- Jingqi Nie
- Shihui Cao (ORCID: https://orcid.org/0000-0003-1066-3708)
- Yanqiu Zhang
- Shipeng Bo
- Nan Wang (ORCID: https://orcid.org/0000-0002-3090-0195)
- Li Yang (ORCID: https://orcid.org/0000-0002-4710-059X)
- Yu Shengmiao
- Chao Shen
Institutions
- Harbin Medical University (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Daqing City People's Hospital (CN)
- Jiaxing University (CN)
Publication Details
- Journal
- Journal of Translational Medicine
- Published
- 2025-10-21
- DOI
- https://doi.org/10.1186/s12967-025-07146-2
- Primary Topic
- Adrenal and Paraganglionic Tumors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Jiaxing University