# P4HA2 contributes to head and neck squamous cell carcinoma progression and EMT through PI3K/AKT signaling pathway

## TL;DR

This study shows that P4HA2 promotes head and neck cancer growth and spread by activating the PI3K/AKT pathway, suggesting it could be a new target for treatment.

## Contribution

The study identifies P4HA2 as a novel driver of HNSCC progression through EMT and PI3K/AKT signaling.

## Key findings

- P4HA2 overexpression increases HNSCC cell proliferation, migration, invasion, and EMT while reducing apoptosis.
- P4HA2 activates the PI3K/AKT pathway, and its effects are reversed by the PI3K inhibitor LY294002.
- High P4HA2 expression correlates with tumor aggressiveness and poor prognosis in HNSCC patients.

## Abstract

Head and neck squamous cell carcinoma (HNSCC) can be defined as a deadly illness with a dismal prognosis in advanced stages. Therefore, we seek to examine P4HA2 expression and effect in HNSCC, along with the underlying mechanisms. This study utilized integrated bioinformatics analyses to evaluate the P4HA2 expression pattern, prognostic implication, and probable function in HNSCC. The study conducted various in vitro experiments, including colony formation, CCK-8, flow cytometry, wound healing, and transwell assays, on the human HNSCC cell line CAL-27 to examine the involvement of P4HA2 in HNSCC progression. Moreover, western blotting was used to investigate epithelial-mesenchymal transition (EMT) markers and PI3K/AKT pathway markers to elucidate the underlying mechanisms. P4HA2 expression was significantly enhanced in HNSCC, and its overexpression was correlated to tumor aggressiveness and a poor prognosis in patients. Based on in vitro experiments, the overexpressed P4HA2 enhanced cell proliferation, migration, invasion, as well as EMT while reducing apoptosis, whereas P4HA2 silencing exhibited the reverse effect. P4HA2 overexpression enhanced PI3K/AKT phosphorylation in HNSCC cells. Moreover, LY294002 was observed to counteract the effects of upregulated P4HA2 on proliferation, migration, invasion, and EMT in HNSCC. Collectively, we indicated that P4HA2 promoted HNSCC progression and EMT via PI3K/AKT signaling pathway.

The online version contains supplementary material available at 10.1007/s12032-024-02358-w.