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Objective <p>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an extremely poor prognosis. While the chaperone-mediated autophagy (CMA) core receptor LAMP-2A and the E3 ubiquitin ligase TRIM23 have garnered attention for their roles in tumorigenesis and immune regulation, their specific functions in PDAC remain insufficiently characterized. This study aims to elucidate the expression patterns and functional roles of LAMP-2A and TRIM23 in pancreatic ductal adenocarcinoma.</p> Methods <p>The expression and prognostic value of LAMP-2A and TRIM23 were evaluated via bioinformatics analysis (TCGA/GEO databases) and validated in clinical PDAC tissues using immunohistochemistry (IHC), immunofluorescence (IF), and Western blotting. Their roles in tumor cell proliferation, migration, and invasion were assessed in vitro using CCK-8 and Transwell assays following gene knockdown or overexpression. A subcutaneous xenograft mouse model and a co-culture system of tumor cells with THP-1-derived macrophages were established to investigate the tumor immune microenvironment. The effects on M1/M2 polarization of tumor-associated macrophages (TAMs) were analyzed by Western blotting, quantitative real-time PCR (qRT-PCR), and ELISA.</p> Results <p>LAMP-2A and TRIM23 were significantly overexpressed in PDAC tissues, and high expression correlated with unfavorable overall survival (OS) and disease-free survival (DFS). Functional assays demonstrated that knockdown of LAMP-2A or TRIM23 markedly suppressed pancreatic cancer cell proliferation, migration, and invasion in vitro and inhibited subcutaneous tumor growth in vivo, whereas LAMP-2A overexpression promoted these malignant phenotypes. Mechanistically, co-culture experiments verified that depletion of LAMP-2A or TRIM23-either in macrophages or in pancreatic cancer cells-effectively reprograms TAMs from a pro-tumor M2 phenotype toward an anti-tumor M1 phenotype, as evidenced by altered expression of TNF-α, ARG1, and other polarization markers.</p> Conclusion <p>In conclusion, LAMP-2A and TRIM23 are upregulated in PDAC and correlate with poor prognosis. Mechanistically, they promote tumor progression partly by driving M2 macrophage polarization. Targeting these two molecules may provide a theoretical basis for developing novel strategies to reverse the immunosuppressive microenvironment of PDAC.</p>

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Expression and functional roles of LAMP-2A and TRIM23 in pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Chunxiu Tan,
  • Ying Yang,
  • Yuanzhen Wang,
  • Jia Wu,
  • Liya Huang

摘要

Objective

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an extremely poor prognosis. While the chaperone-mediated autophagy (CMA) core receptor LAMP-2A and the E3 ubiquitin ligase TRIM23 have garnered attention for their roles in tumorigenesis and immune regulation, their specific functions in PDAC remain insufficiently characterized. This study aims to elucidate the expression patterns and functional roles of LAMP-2A and TRIM23 in pancreatic ductal adenocarcinoma.

Methods

The expression and prognostic value of LAMP-2A and TRIM23 were evaluated via bioinformatics analysis (TCGA/GEO databases) and validated in clinical PDAC tissues using immunohistochemistry (IHC), immunofluorescence (IF), and Western blotting. Their roles in tumor cell proliferation, migration, and invasion were assessed in vitro using CCK-8 and Transwell assays following gene knockdown or overexpression. A subcutaneous xenograft mouse model and a co-culture system of tumor cells with THP-1-derived macrophages were established to investigate the tumor immune microenvironment. The effects on M1/M2 polarization of tumor-associated macrophages (TAMs) were analyzed by Western blotting, quantitative real-time PCR (qRT-PCR), and ELISA.

Results

LAMP-2A and TRIM23 were significantly overexpressed in PDAC tissues, and high expression correlated with unfavorable overall survival (OS) and disease-free survival (DFS). Functional assays demonstrated that knockdown of LAMP-2A or TRIM23 markedly suppressed pancreatic cancer cell proliferation, migration, and invasion in vitro and inhibited subcutaneous tumor growth in vivo, whereas LAMP-2A overexpression promoted these malignant phenotypes. Mechanistically, co-culture experiments verified that depletion of LAMP-2A or TRIM23-either in macrophages or in pancreatic cancer cells-effectively reprograms TAMs from a pro-tumor M2 phenotype toward an anti-tumor M1 phenotype, as evidenced by altered expression of TNF-α, ARG1, and other polarization markers.

Conclusion

In conclusion, LAMP-2A and TRIM23 are upregulated in PDAC and correlate with poor prognosis. Mechanistically, they promote tumor progression partly by driving M2 macrophage polarization. Targeting these two molecules may provide a theoretical basis for developing novel strategies to reverse the immunosuppressive microenvironment of PDAC.