EGFR and PGE2 signaling pathways mutually cooperate to promote pro-tumorigenic effects in cervical cancer.

Authors

Vitória R de Azevedo, Isabella Dos S Guimarães, Mario J Farrapo, Karina Martins-Cardoso, Andréia C de Melo, Robson Q Monteiro, Vitor H de Almeida

Published in

Biochimica et biophysica acta. Molecular basis of disease. Pages 168443. Aug 30, 2026. Epub Aug 30, 2026.

Abstract

Cervical cancer (CC) remains a public health challenge in developing countries. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase highly expressed in CC. Studies showed that PGE2 may transactivate EGFR in some models. However, understanding the interaction between the EGFR and PGE2 signaling pathways in CC is a key area for investigation.
The Cancer Genome Atlas (TCGA) was used to evaluate gene expression correlation and clinical outcomes. Panitumumab and aspirin were employed to inhibit EGFR and COX-1/2, respectively. Cell migration was evaluated using Boyden chamber. MTT and clonogenic assays determined cell viability and clonogenicity. Western Blotting analyzed protein expression. PGE2 was measured in the supernatants of cell lines using ELISA. Flow cytometry was used for cell death assays.
TCGA analysis revealed a significant positive correlation between EGFR and COX-1, COX-2, and microsomal prostaglandin E synthase-1 (mPGES-1). CC patients showed decreased overall survival upon overexpression of EGFR or COX-2. CASKI and HeLa cells were cisplatin-resistant, whereas C33A cells were chemosensitive. CASKI cells exhibited the highest EGFR levels, while HeLa cells showed highest levels of COX-2 and mPGES-1. HeLa cells showed marked upregulation of COX-2 and mPGES-1 and increased PGE2 secretion upon EGF stimulation. Moreover, PGE2 activated ERK signaling and promoted cell migration through an EGFR-dependent mechanism. Panitumumab plus aspirin impaired cell viability, clonogenicity and chemoresistance. Simultaneous stimulation with EGF and PGE2 mitigated cisplatin-induced apoptosis in CASKI cells.
The interactions between EGFR and PGE2 signaling pathways link inflammation and oncogenic signaling, promoting tumor aggressive behavior.

PMID:
42669370
Bibliographic data and abstract were imported from PubMed on 31 Aug 2026.

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