# PLOD2 promotes proliferation, migration and invasion of colorectal cancer cells via PI3K-AKT-GSK3β signaling pathway

## TL;DR

This study shows that PLOD2 promotes colorectal cancer cell growth and spread by activating the PI3K-AKT-GSK3β pathway.

## Contribution

The study reveals a novel role of PLOD2 in CRC progression via the PI3K-AKT-GSK3β signaling pathway.

## Key findings

- PLOD2 overexpression increases CRC cell proliferation, migration, and invasion.
- PLOD2 interacts with PI3K to activate the PI3K-AKT-GSK3β pathway in CRC cells.
- PI3K inhibitors reverse PLOD2-mediated effects on CRC progression.

## Abstract

Colorectal cancer (CRC) progression critically depends on the tumor microenvironment. PLOD2, an enzyme involved in collagen biosynthesis, is highly expressed in many cancers. While it promotes CRC growth via the USP15–AKT/mTOR pathway, its role in enhancing tumor cell migration and invasion remains unclear. Our study identified a significant upregulation of PLOD2 in colorectal cancer. This upregulation was closely associated with clinical stage, lymph node metastasis, and nerve invasion in CRC. Functional assays, including CCK-8, colony formation, wound healing, and Transwell migration and invasion assays, showed that PLOD2 overexpression enhanced CRC cell proliferation, migration, and invasion, while PLOD2 silencing exerted the opposite effects. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that PLOD2 may influence CRC progression via the PI3K-AKT signaling pathway. Co-immunoprecipitation assays demonstrated that PLOD2 was co-precipitated with PI3K, confirming their interaction. Additionally, rescue experiments showed that the PI3K inhibitor LY294002 and the agonist 740Y-P could reverse PLOD2-mediated effects on CRC cell proliferation, migration, and invasion. This study demonstrates that PLOD2 promotes the proliferation, migration, and invasion of CRC cells by interacting with PI3K to activate the PI3K-AKT-GSK3β signaling pathway.

The online version contains supplementary material available at 10.1038/s41598-026-38593-6.