# Beyond Tumor Suppression: The Multifaceted Functions of HOPX in Tissue Differentiation, Metabolism, and Immunity

## TL;DR

This paper reviews the diverse roles of HOPX, a transcription factor, in tissue development, cancer suppression, metabolism, and immunity, suggesting its potential in cancer immunotherapy.

## Contribution

The paper highlights the dual role of HOPX in epithelial and mesenchymal cancers and its emerging roles in immunity and metabolism.

## Key findings

- HOPX acts as a tumor suppressor in epithelial-derived carcinomas but promotes sarcomas.
- HOPX is involved in immune cell differentiation and tumor microenvironment regulation.
- HOPX influences lipid metabolism and may serve as a potential target for tumor immunotherapy.

## Abstract

The transcription factor homeodomain-only protein X (HOPX) is the smallest member of the homeodomain protein family. Lacking a DNA-binding domain, it acts as a co-effector, interacting with other transcription factors such as serum response factor (SRF) and GATA-binding factor 6 (GATA6) to regulate the differentiation and development of the heart and lung. HOPX exerts a tumor-suppressive function in various types of epithelial-derived carcinoma, while it promotes oncogenic effects in mesenchymal-derived sarcoma, indicating a distinct role of HOPX in the two major types of the malignancy. In addition, accumulating evidence shows that HOPX is expressed in the immune system and involved in the differentiation of immune cells. Recently, the emerging role of HOPX in metabolism has gained attention. This review describes the identification of HOPX in various tissues and discusses its role in carcinogenesis, as well as its functions in tissue differentiation, lipid metabolism, immunity, and the tumor microenvironment. The participation of HOPX in carcinogenesis and immunity implies that it may serve as a potential enhancer in tumor immunotherapy.