# The Association of Aquaporins with MAPK Signaling Pathway Unveils Potential Prognostic Biomarkers for Pancreatic Cancer: A Transcriptomics Approach

**Authors:** Inês V. da Silva, Paula A. Lopes, Elisabete Fonseca, Emanuel Vigia, Jorge Paulino, Graça Soveral

PMC · DOI: 10.3390/biom15040488 · Biomolecules · 2025-03-26

## TL;DR

This study explores how aquaporins interact with cancer signaling pathways in pancreatic tumors, identifying potential biomarkers for early detection and prognosis.

## Contribution

The study reveals novel correlations between specific aquaporins and MAPK signaling components in pancreatic cancer tissues.

## Key findings

- AQP3 correlates strongly with c-Jun in pancreatic tumors.
- AQP5 correlates with CDH1/EGFR in tumors but not in healthy tissues.
- Findings were confirmed in vitro using BxPC3 pancreatic cancer cells.

## Abstract

Pancreatic cancer is one of the most lethal and challenging malignancies. Its severity is primarily linked to the constitutively activated mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. Aquaporins (AQPs) are frequently overexpressed in pancreatic cancer, playing crucial roles in cell signaling, and consequently promoting cell migration, proliferation, and invasion. Here, we investigate the transcriptomics of key players in epithelial–mesenchymal transition (EMT) and the MAPK/ERK signaling pathway in pancreatic cancer tissues, correlating them with tumor AQP expression to highlight their potential as diagnostic or prognostic tools. The transcriptomics analysis was conducted in 24 paired pancreatic tumors and adjacent healthy tissues, and analyses were performed considering the patients’ age and gender, as well as tumor invasiveness and aggressiveness. Our results revealed strong positive Pearson correlation coefficients between AQP3 and c-Jun, and between AQP5 and CDH1/EGFR in pancreatic tumors but not in healthy tissues, with posterior in vitro confirmation in pancreatic cancer BxPC3 cells, suggesting a shift in the regulatory mechanisms of gene expression that certainly affect the physiology of the tissue, influencing cancer initiation and progression. This study underscores the interplay between AQPs and cancer signaling pathways, opening new avenues for defining novel clinical biomarkers and improving the early detection of pancreatic cancer.

## Linked entities

- **Genes:** AQP3 (aquaporin 3 (Gill blood group)) [NCBI Gene 360], AQP5 (aquaporin 5) [NCBI Gene 362], JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725], CDH1 (cadherin 1) [NCBI Gene 999], EGFR (epidermal growth factor receptor) [NCBI Gene 1956]
- **Diseases:** pancreatic cancer (MONDO:0005192)

## Full-text entities

- **Genes:** CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, AQP3 (aquaporin 3 (Gill blood group)) [NCBI Gene 360] {aka AQP-3, GIL}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, AQP5 (aquaporin 5) [NCBI Gene 362] {aka AQP-5, PPKB}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}
- **Diseases:** cancer (MESH:D009369), Pancreatic Cancer (MESH:D010190)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** BxPC3 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0186)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12024632/full.md

## References

78 references — full list in the complete paper: https://tomesphere.com/paper/PMC12024632/full.md

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Source: https://tomesphere.com/paper/PMC12024632