The latest research published in Genes & Diseases unveils groundbreaking insights into the role of the aging process and the associated factor EMP1 in the progression of resectable pancreatic cancer (PC). The study, conducted by a team of researchers from the University of Chinese Academy of Sciences and Chongqing Medical University, has established a prognostic model that links EMP1 expression with adverse clinical outcomes, particularly among older PC patients.

Pancreatic cancer remains a highly aggressive malignancy with limited treatment options, especially in its resectable form. This study highlights how aging, characterized by systemic and microenvironmental changes, significantly contributes to tumor growth and metastasis. The researchers developed an Age-Related Score (ARS) system, integrating bulk RNA-seq and single-cell RNA-seq data, to predict prognosis in postoperative PC patients. A key finding of the study is the identification of EMP1 as a pivotal molecule within this system, significantly correlating with poor survival outcomes.

In both in vitro and in vivo experiments, increased EMP1 expression was shown to promote cell proliferation, migration, and invasion by activating the PI3K/AKT signaling pathway. Using cellular trajectory analysis, the study demonstrated that PC cells with high ARS scores and elevated EMP1 levels exhibited enhanced aging and epithelial-mesenchymal transition (EMT) capabilities, indicating a more aggressive tumor phenotype. Furthermore, the EMP1-driven activation of the PI3K/AKT pathway was identified as a major contributor to the oncogenic potential of pancreatic cancer cells.

The team’s in vivo studies using subcutaneous, pulmonary metastasis, and orthotopic pancreatic liver metastasis models in mice corroborated these findings. Mice with EMP1 knockdown exhibited reduced tumor volume and metastasis, while EMP1 overexpression led to increased tumor growth and metastatic spread. Importantly, the application of the PI3K/AKT pathway inhibitor LY294002 successfully reversed the oncogenic effects induced by EMP1, suggesting a potential therapeutic avenue.

These findings not only establish EMP1 as an independent risk factor for poor prognosis in PC patients but also propose targeted therapy against EMP1 and the PI3K/AKT pathway as a promising strategy to mitigate tumor progression. Future studies focusing on the immune microenvironment and detailed mechanistic pathways are essential to further elucidate EMP1’s role and to develop age-specific anti-cancer interventions.
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Reference
Junfeng Zhang, Jianyou Gu, Tao Zhang, Renpei Xia, Jianbo Li, Mingda Tan, Yongjun Yang, Jifeng Xiang, Bin Xie, Rong Tang, Wangge Li, Xianxing Wang, Shixiang Guo, Huaizhi Wang, The role of the aging process and related factor EMP1 in promoting progression of resectable pancreatic cancer, Genes & Diseases, Volume 12, Issue 5, 2025, 101490, https://doi.org/10.1016/j.gendis.2024.101490

Funding Information:
Natural Science Foundation of Chongqing, China CSTB2022NSCQ-MSX1339
Natural Science Foundation of Chongqing, China CSTB2022NSCQ-MSX1273
Foundation of Key Laboratory of Tumor Immunology and Pathology (Army Medical University), Ministry of Education 2023jsz910
National Natural Science Foundation of China 82203165
National Natural Science Foundation of China 82072723,
National Natural Science Foundation of China 82103249
Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) 2022MSXM031
Chongqing Technology Innovation and Application Development Special Key Project CSTB2022TIAD-KPX0170