# S100A14 Facilitates Pancreatic Cancer Progression via S100A16-Mediated p53 Suppression

## TL;DR

This study shows that S100A14 promotes pancreatic cancer by stabilizing S100A16 and suppressing p53, suggesting a new therapeutic target.

## Contribution

The study reveals a novel regulatory axis involving S100A14, S100A16, and p53 in pancreatic cancer progression.

## Key findings

- S100A14 is upregulated in pancreatic cancer and acts as a key prognostic gene.
- S100A14 stabilizes S100A16 protein, which suppresses p53 and p21 expression.
- Knockdown of S100A14 reverses cancer cell metastasis and enhances apoptosis.

## Abstract

Pancreatic cancer (PC) is characterized by poor prognosis due to its limited treatment choices and delayed detection. S100A14 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 S100A14 in PC progression.

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.

S100A14 was markedly upregulated in PC tissues and cell lines and identified as a key prognostic gene. Silencing S100A14 suppressed EMT, proliferation, invasion, and migration, while reversing S100A16-mediated p53 inhibition and enhancing apoptosis. Mechanistically, Co-IP assay confirmed the protein interaction between S100A14 and S100A16; S100A14 stabilized S100A16 protein through post-translational modification without transcriptional regulation; the S100A14/S100A16 axis reduced p53 protein stability and inhibited its transcriptional activity as well as the downstream p21 expression. Critically, knockdown of S100A14 abrogated the pro-metastatic phenotype of cancer cells.

This study identifies S100A14 promotes PC progression by stabilizing S100A16 and suppressing the tumor-suppressive p53/p21 pathway; knockdown of S100A14 can reverse the above effects, restore p53 function, and enhance cancer cell apoptosis. Targeting the S100A14/S100A16/p53 regulatory axis could represent a promising therapeutic approach for PC.