@Article{or.2025.070207,
AUTHOR = {Pingping Hu, Zhenhao Fei, Jianhua Bai, Zhiwen Wang, Yun Jin},
TITLE = {<i>S100A14</i> Facilitates Pancreatic Cancer Progression via <i>S100A16</i>-Mediated <i>p53</i> Suppression},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {3},
PAGES = {--},
URL = {http://www.techscience.com/or/v34n3/66260},
ISSN = {1555-3906},
ABSTRACT = { <b>Objectives:</b> Pancreatic cancer (PC) is characterized by poor prognosis due to its limited treatment choices and delayed detection. <i>S100A14</i> has been implicated in tumor progression, yet its regulatory hierarchy and functional interplay in PC remain unclear. This study aimed to define the role of <i>S100A14</i> in PC progression. <b>Methods:</b> Integrated bioinformatic analyses of TCGA-PAAD and GSE22780 datasets identified candidate hub genes. Prognostic relevance was assessed via Kaplan-Meier and ROC analyses. Functional experiments were performed in PANC-1 and BxPC-3 cells, including qRT-PCR, CCK-8 assay, Western blotting, Transwell assay, and apoptosis assay. Co-immunoprecipitation (Co-IP) was used to verify S100A14–S100A16 interaction. CHX chase and dual-luciferase assays were employed to assess protein stability and transcriptional activity. <b>Results:</b> <i>S100A14</i> was markedly upregulated in PC tissues and cell lines and identified as a key prognostic gene. Silencing <i>S100A14</i> suppressed EMT, proliferation, invasion, and migration, while reversing <i>S100A16</i>-mediated p53 inhibition and enhancing apoptosis. Mechanistically, Co-IP assay confirmed the protein interaction between <i>S100A14</i> and <i>S100A16</i>; <i>S100A14</i> stabilized <i>S100A16</i> protein through post-translational modification without transcriptional regulation; the <i>S100A14/S100A16</i> axis reduced <i>p53</i> protein stability and inhibited its transcriptional activity as well as the downstream <i>p21</i> expression. Critically, knockdown of <i>S100A14</i> abrogated the pro-metastatic phenotype of cancer cells. <b>Conclusion:</b> This study identifies <i>S100A14</i> promotes PC progression by stabilizing <i>S100A16</i> and suppressing the tumor-suppressive <i>p53/p21</i> pathway; knockdown of <i>S100A14</i> can reverse the above effects, restore <i>p53</i> function, and enhance cancer cell apoptosis. Targeting the <i>S100A14/S100A16/p53</i> regulatory axis could represent a promising therapeutic approach for PC.},
DOI = {10.32604/or.2025.070207}
}