The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications

Sep 24, 2026

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Tumor initiation, progression, and response to therapies depend heavily on interactions between malignant cells and the tumor microenvironment (TME), including cancer/non-cancer cells, cytokines, chemokines, and multiple surrounding factors. Cancer and stromal cells can adapt to the TME and reshape it through signaling pathways. The post-translational modification SUMOylation is highlighted as a key flexible mechanism governing tumorigenesis-related processes such as chromatin organization, DNA repair, transcription, trafficking, and signal conduction. This review analyzes SUMOylation’s roles in TME formation and reprogramming and evaluates therapeutic targeting, including SUMOylation inhibitors (SUMOi), for improving tumor prognosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Abstract

Background

Protein PTMs and cancer

SUMOylation and TME reprogramming

Clinical and therapeutic targeting

SUMOylation inhibitors (SUMOi)

Gu et al. Experimental Hematology & Oncology (2023) 12:58 [https://doi.org/10.1186/s40164-023-00420-3](https://doi.org/10.1186/s40164-023-00420-3) Experimental Hematology & Oncology REVIEW Open Access The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications Yunru Gu1†, Yuan Fang1†, Xi Wu1†, Tingting Xu1†, Tong Hu1, Yangyue Xu1, Pei Ma1*, Qiang Wang3* and Yongqian Shu1,2* Abstract Tumor initiation, progression, and response to therapies depend to a great extent on interactions between malignant cells and the tumor microenvironment (TME), which denotes the cancerous/non-cancerous cells, cytokines, chemokines, and various other factors around tumors. Cancer cells as well as stroma cells can not only obtain adaption to the TME but also sculpt their microenvironment through a series of signaling pathways. The post-translational modification (PTM) of eukaryotic cells by small ubiquitin-related modifier (SUMO) proteins is now recognized as a key flexible pathway. Proteins involved in tumorigenesis guiding several biological processes including chromatin organization, DNA repair, transcription, protein trafficking, and signal conduction rely on SUMOylation. The purpose of this review is to explore the role that SUMOylation plays in the TME formation andreprogramming, emphasize the importance of targeting SUMOylation to intervene in the TME and discuss the potential of SUMOylation inhibitors (SUMOi) in ameliorating tumor prognosis. Keywords Tumor microenvironment, Post-translational modification, SUMOylation, Hypoxia, Metabolism, Inflammation, Immune response, Clinical implications †Yunru Gu, Yuan Fang, Xi Wu, and Tingting Xu have contributed equally to this work. *Correspondence: Pei Ma[mapei@njmu.edu.cn](mapei@njmu.edu.cn)[ ](mapei@njmu.edu.cn)Qiang Wang [wangqiang@ahmu.edu.cn](wangqiang@ahmu.edu.cn)[ ](wangqiang@ahmu.edu.cn)Yongqian Shu [yongqian_shu@163.com](yongqian_shu@163.com); [shuyongqian@csco.org.cn](shuyongqian@csco.org.cn) 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, People’s Republic of China 2Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui Province, People’s Republic of China Background Over the past decade, the variety of protein PTMs has rapidly increased. PTMs alter targeted proteins’ conformation, charge state, and hydrophobicity, affecting their stability and activity. Diverse genomic and proteomic alterations are required in the process that a normal cell converts to a malignant one. Several dysregulated PTM pathways can result in cancer cell proliferation and metastasis. Nowadays, hundreds of unique PTMs in eukaryotic cells have sprung up, such as acetylation, phosphorylation, ubiquitination, and SUMOylation. PTM with SUMO, named SUMOylation, was discovered in the middle of the 1990s [1]. Observed in numerous human pathologies, particularly in tumorigenesis and progression, SUMOylation acts in various aspects of cell © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will

FAQs

What does SUMOylation regulate in tumor cells and the tumor microenvironment?

Proteins involved in tumorigenesis use SUMOylation to influence chromatin organization, DNA repair, transcription, protein trafficking, and signal conduction, thereby affecting TME formation and reprogramming.

Why is the tumor microenvironment important for cancer progression and therapy response?

Interactions between malignant and surrounding non-malignant cells, along with cytokines, chemokines, and other local factors, shape tumor initiation, progression, and how tumors respond to therapies.

How can targeting SUMOylation improve cancer prognosis?

The review emphasizes intervening in TME through SUMOylation targeting and discusses the potential of SUMOylation inhibitors (SUMOi) to ameliorate tumor prognosis.

Sep 24, 2026

Uploaded by Connor