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journal article·2026-05-19Open access

Aptamer‐Targeted PrPC Drives Colorectal Cancer Metastasis via a LYN‐STAT3 Complex and Enables Liquid Biopsy Detection

Chunlin Wang, Hongyu Wu, Chaojing Zheng, Hao Zhang, Xiaoqiu Wu, Jiaqi Wang, Zewen Chang, Jun Xiang, Yunxiao Liu, Chenkai Zhang, Yuliuming Wang, Hao Jiang, Yuchen Zhong, Jun Luo, Ying Chen, NaNa Zhang, Weiyuan Zhang, Ziming Yuan, ChaoXia Zou, Weihong Tan, Meng Wang, Hanqing Hu, Tao Bing, Guiyu Wang

Advanced Science
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Abstract

ABSTRACT Colorectal cancer (CRC) poses a significant global health challenge, highlighting the need for better diagnostic tools and molecular targets. Compared to traditional antibodies, aptamers, which are single‐stranded oligonucleotides with high affinity and low immunogenicity, offer an ideal platform for discovering novel biomarkers. Based on this approach, we used the Cell‐SELEX strategy to develop a high‐affinity aptamer‐based probe, WHY‐3E, which successfully identified the cellular prion protein (PrPC) as a key molecular target. We observed that PrPC was significantly upregulated in CRC tissues, strongly correlating with unfavorable clinical outcomes. Functionally, PrPC promotes malignant phenotypes, including migration and invasion, by regulating MSN. Mechanistically, we revealed that PrPC physically translocates from the cell surface to the cytoplasm via endocytosis. Once internalized, it interacts with the STAT3‐NTD and LYN‐SH domains, facilitating the ternary complex formation that enhances LYN‐mediated STAT3 phosphorylation, ultimately increasing MSN transcriptional activity. Moreover, the deubiquitinase USP18 stabilizes PrPC by removing its Lys48‐linked ubiquitin chains, ensuring the continuous activation of this oncogenic axis. Notably, the WHY‐3E aptamer achieved 90.6% sensitivity and 89.0% specificity in detecting PrPC‐positive circulating exosomes in patient cohorts. These findings deepen the mechanistic understanding of CRC progression and offer novel strategic avenues for PrPC‐targeted aptamer applications in non‐invasive diagnostics.
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Research context

OpenAlex topics: Prion Diseases and Protein Misfolding · Advanced biosensing and bioanalysis techniques · Nuclear Structure and Function

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Colorectal Cancer Surgery The Second Affiliated Hospital of Harbin Medical University Harbin Heilongjiang P. R. China

The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou Zhejiang P. R. China

Molecular Science and Biomedicine Laboratory (MBL) State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Aptamer Engineering Center of Hunan Province Hunan University Changsha Hunan P. R. China

Department of Thoracic Surgery Fujian Medical University Union Hospital Fuzhou Fujian P. R. China

Department of General Surgery The Fourth Affiliated Hospital of Harbin Medical University Harbin Heilongjiang P. R. China

Cancer Center Department of Medical Oncology Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College Hangzhou Zhejiang P. R. China

Department of Colorectal Cancer Surgery Zhejiang Cancer Hospital Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou Zhejiang P. R. China

Department of Pathology The Second Affiliated Hospital of Harbin Medical University Harbin Heilongjiang P. R. China

Department of Biochemistry and Molecular Biology Harbin Medical University Harbin Heilongjiang P. R. China

Funding

National Natural Science Foundation of China

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