# Arginase 2 Promotes Colorectal Cancer Metastasis via PI3K/AKT Pathway Activation and Regulates Tumor Immune Infiltration

## TL;DR

This study shows that high levels of Arginase 2 in colorectal cancer tissues are linked to worse outcomes and cancer spread, offering a potential new target for treatment.

## Contribution

The study identifies ARG2 as a novel prognostic marker and therapeutic target in CRC through its role in EMT, PI3K/AKT signaling, and immune infiltration.

## Key findings

- ARG2 is upregulated in CRC tissues and correlates with poor prognosis.
- ARG2 knockdown reduces CRC cell proliferation, migration, and invasion by suppressing EMT and PI3K/AKT signaling.
- High ARG2 expression is associated with reduced immune cell infiltration and decreased chemotherapy efficacy.

## Abstract

Colorectal cancer (CRC) is a leading cause of cancer‐related deaths, with metabolic reprogramming involved in its pathogenesis. Aberrant Arginase 2 (ARG2) expression is linked to malignant progression, but its role in CRC remains unclear.

ARG2 expression in CRC and adjacent tissues was analyzed. In vitro experiments were performed after ARG2 knockdown. Mechanistic investigations focused on epithelial‐mesenchymal transition (EMT), PI3K/AKT pathway, immune infiltration, and drug sensitivity.

ARG2 was upregulated in CRC tissues, correlating with poor prognosis. ARG2 knockdown inhibited CRC cell proliferation, migration, and invasion by reducing Zinc Finger E‐Box Binding Homeobox 1 (ZEB1), N‐cadherin, and MMP2, suppressing EMT. Additionally, ARG2 knockdown significantly inhibited the PI3K/AKT signaling pathway. Immune infiltration analysis revealed high ARG2 expression correlated with reduced activated B cells and macrophages. Drug sensitivity analysis indicated that high ARG2 expression was associated with decreased efficacy of certain chemotherapeutic agents.

ARG2 is an independent prognostic marker for CRC. It promotes CRC progression via regulating EMT and PI3K/AKT, holding potential as a novel diagnostic and therapeutic target.