TP53 status is associated with differential stress-marker expression and APP maturation in colon cancer cells.

Authors

Hye Joung Choi, Suk Jun Song, Huu Dat Nguyen, Thanh Trung Nguyen, Hoang Bao Tram Tran, Jung Hyun Lim, Young Eun Kim

Published in

Molecular biology reports. Volume 53. Issue 1. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

The systemic influence of tumor-derived secretomes on the nervous system remains poorly understood. We investigated whether differences in TP53 status are associated with altered cellular stress-handling states and amyloid precursor protein (APP) processing in colon cancer cells.
APP maturation, intracellular localization, and stress-associated signaling were analyzed in TP53 wild-type and TP53-mutant colon cancer cells using immunoblotting, confocal microscopy, and ELISA. Functional associations between APP processing, GPX4-associated pathways, and neurotoxicity were further evaluated using pharmacological and genetic perturbation approaches, followed by conditioned-medium transfer experiments in HT22 neuronal and BV2 microglial cells.
Distinct patterns of APP maturation and intracellular localization were observed between colon cancer cells with different TP53 status. TP53-mutant cells preferentially processed APP into its mature form and displayed relatively higher GPX4 expression, whereas TP53 wild-type cells exhibited increased endoplasmic reticulum (ER) retention of immature APP, accompanied by reduced GPX4 and elevated ATF4 expression. Functional analyses further revealed that these distinct intracellular stress-associated states were accompanied by differential neurotoxic effects of tumor-derived conditioned media. Conditioned media derived from TP53 wild-type cells significantly reduced cell viability, decreased attached-cell density, and induced morphological deterioration in HT22 neuronal and BV2 microglial cells. In contrast, conditioned media derived from TP53-mutant cells exhibited comparatively reduced neurotoxicity. Conditioned media derived from isogenic TP53-null cells displayed similarly reduced neurotoxicity, further supporting an association between TP53 status and secretome-associated phenotypes.
Collectively, our findings suggest that differences in TP53 status are associated with distinct stress-associated signaling, APP maturation, and secretome-associated phenotypes, which may contribute to differential tumor-neural cross-talk mediated by tumor-derived secretomes.

PMID:
42579179
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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