# The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma

## TL;DR

TSHZ3 is a transcription factor that suppresses tumor growth and metastasis in lung adenocarcinoma by boosting immune responses and reducing cancer spread.

## Contribution

This study reveals TSHZ3's novel role in tumor suppression through immune modulation and inhibition of metastasis in LUAD.

## Key findings

- TSHZ3 expression is lower in LUAD tissues and linked to better patient survival.
- TSHZ3 inhibits cancer cell migration, invasion, and EMT while promoting apoptosis via CD86+ macrophages.
- TSHZ3 increases CCL2 and CCR2 expression, suggesting a role in M1 macrophage recruitment.

## Abstract

Teashirt zinc finger homeobox 3 (TSHZ3) is a transcription factor implicated in the progression of certain cancers. However, its expression and function in lung adenocarcinoma (LUAD) remain unclear. Therefore, we aimed to investigate TSHZ3 expression and assess its prognostic significance in LUAD patients. First, we explored prognostic data and predicted the function of TSHZ3 in lung cancer through bioinformatics analysis. We then validated the functions using cellular and animal experiments. Our results indicated that TSHZ3 expression was significantly lower in LUAD compared to normal lung tissues. High TSHZ3 expression was positively associated with better overall survival in LUAD patients. GO and pathway analyses suggested that TSHZ3 is involved in immune responses and various cancer-related processes. Immune infiltration analysis revealed correlations between TSHZ3 and immune cell infiltration, particularly macrophages, as well as the expression of numerous immune stimulators, chemokines, and receptors. Our experiment results suggest that TSHZ3 overexpression inhibits cell migration, invasion, and epithelial–mesenchymal transition (EMT) in vivo and in vitro. LUAD cells overexpressing TSHZ3 were more prone to apoptosis due to the recruitment of CD86+ macrophages. In addition, CCL2 expression was significantly higher in LUAD cells overexpressing TSHZ3, while CCR2 expression was also significantly upregulated in co-cultured macrophages. These findings suggest that TSHZ3 is an important tumor suppressor by inhibiting EMT and metastasis while inducing apoptosis through M1 macrophage chemotaxis via the CCL2/CCR2.