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Volume 14
Issue 21
10.3390/cells14211718
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Review

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

by
Fabian Munzert
1,
Miljana Nenkov
1,
Alexander Berndt
1,2,
Tim Sandhaus
3,
Susanne Lang
4,
Nikolaus Gaßler
1,2 and
Yuan Chen
1,*
1
Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
2
ThIMEDOP—CeTraMed, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
3
Clinic of Cardiothoracic Surgery, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
4
Department of Internal Medicine V, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
*
Author to whom correspondence should be addressed.
Cells 2025, 14(21), 1718; https://doi.org/10.3390/cells14211718
Submission received: 8 September 2025 / Revised: 15 October 2025 / Accepted: 29 October 2025 / Published: 1 November 2025
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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.
Keywords: HOPX; homeodomain protein; tissue differentiation; metabolism; tumor suppression; immunity; tumor immunotherapy HOPX; homeodomain protein; tissue differentiation; metabolism; tumor suppression; immunity; tumor immunotherapy

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MDPI and ACS Style

Munzert, F.; Nenkov, M.; Berndt, A.; Sandhaus, T.; Lang, S.; Gaßler, N.; Chen, Y. Beyond Tumor Suppression: The Multifaceted Functions of HOPX in Tissue Differentiation, Metabolism, and Immunity. Cells 2025, 14, 1718. https://doi.org/10.3390/cells14211718

AMA Style

Munzert F, Nenkov M, Berndt A, Sandhaus T, Lang S, Gaßler N, Chen Y. Beyond Tumor Suppression: The Multifaceted Functions of HOPX in Tissue Differentiation, Metabolism, and Immunity. Cells. 2025; 14(21):1718. https://doi.org/10.3390/cells14211718

Chicago/Turabian Style

Munzert, Fabian, Miljana Nenkov, Alexander Berndt, Tim Sandhaus, Susanne Lang, Nikolaus Gaßler, and Yuan Chen. 2025. "Beyond Tumor Suppression: The Multifaceted Functions of HOPX in Tissue Differentiation, Metabolism, and Immunity" Cells 14, no. 21: 1718. https://doi.org/10.3390/cells14211718

APA Style

Munzert, F., Nenkov, M., Berndt, A., Sandhaus, T., Lang, S., Gaßler, N., & Chen, Y. (2025). Beyond Tumor Suppression: The Multifaceted Functions of HOPX in Tissue Differentiation, Metabolism, and Immunity. Cells, 14(21), 1718. https://doi.org/10.3390/cells14211718

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