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Posttranslational control of lipogenesis in the tumor microenvironment.
Literature Information
| DOI | 10.1186/s13045-022-01340-1 |
|---|---|
| PMID | 36038892 |
| Journal | Journal of hematology & oncology |
| Impact Factor | 40.4 |
| JCR Quartile | Q1 |
| Publication Year | 2022 |
| Times Cited | 18 |
| Keywords | Cancer, Lipid metabolism reprogramming, Posttranslational modification, Tumor microenvironment |
| Literature Type | Journal Article, Review, Research Support, Non-U.S. Gov't |
| ISSN | 1756-8722 |
| Pages | 120 |
| Issue | 15(1) |
| Authors | Yahui Zhu, Xingrong Lin, Xiaojun Zhou, Edward V Prochownik, Fubing Wang, Youjun Li |
TL;DR
This review discusses the metabolic reprogramming of cancer cells, particularly the alterations in lipid metabolism that are characteristic of aggressive tumors and associated with poor prognosis. It highlights the role of posttranslational modifications (PTMs) of lipid metabolism-related enzymes in facilitating these metabolic changes within the tumor microenvironment, emphasizing the significance of understanding these mechanisms for developing targeted cancer therapies.
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Cancer · Lipid metabolism reprogramming · Posttranslational modification · Tumor microenvironment
Abstract
Metabolic reprogramming of cancer cells within the tumor microenvironment typically occurs in response to increased nutritional, translation and proliferative demands. Altered lipid metabolism is a marker of tumor progression that is frequently observed in aggressive tumors with poor prognosis. Underlying these abnormal metabolic behaviors are posttranslational modifications (PTMs) of lipid metabolism-related enzymes and other factors that can impact their activity and/or subcellular localization. This review focuses on the roles of these PTMs and specifically on how they permit the re-wiring of cancer lipid metabolism, particularly within the context of the tumor microenvironment.
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Primary Questions Addressed
- What specific posttranslational modifications are most impactful on lipid metabolism-related enzymes in cancer cells?
- How do different types of tumors influence the patterns of lipid metabolism in their microenvironments?
- In what ways can targeting posttranslational modifications of lipid metabolism enzymes serve as a therapeutic strategy in cancer treatment?
- How does the tumor microenvironment alter the expression and function of lipid metabolism enzymes through posttranslational mechanisms?
- What are the implications of altered lipid metabolism on the immune response within the tumor microenvironment?
Key Findings
Research Background and Objectives
The review by Zhu et al. focuses on the metabolic reprogramming of cancer cells, particularly the alterations in lipid metabolism within the tumor microenvironment (TME). It highlights the significance of posttranslational modifications (PTMs) of lipid metabolism-related enzymes, which play a crucial role in tumor progression and provide potential therapeutic targets.
Main Methods/Materials/Experimental Design
The review synthesizes existing literature on lipid metabolism in cancer, detailing various mechanisms and pathways involved. The authors emphasize the role of PTMs in regulating lipid metabolism, categorizing them into several types: phosphorylation, acetylation, ubiquitination, SUMOylation, and methylation.
Technical Route (Mermaid Code)
Key Results and Findings
- Lipid Metabolism Alterations: Cancer cells exhibit increased lipid uptake and de novo synthesis, which supports their rapid growth and proliferation.
- Role of PTMs: PTMs of enzymes such as SREBP1, ACC, and FASN are critical for regulating lipid metabolism in cancer cells. For example, phosphorylation and acetylation can either promote or inhibit enzyme activity, impacting tumor growth.
- TME Influence: The TME significantly affects lipid metabolism, with tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) influencing lipid uptake and storage, further promoting tumor progression.
Main Conclusions/Significance/Innovativeness
The review underscores the complex interplay between lipid metabolism and cancer progression, driven by PTMs of metabolic enzymes. It proposes that targeting lipid metabolism and its regulatory mechanisms can offer novel therapeutic strategies for cancer treatment. This approach could lead to more effective therapies by exploiting the unique metabolic dependencies of cancer cells.
Research Limitations and Future Directions
- Limitations: The review is primarily a synthesis of existing literature and lacks original experimental data. The complexity of lipid metabolism and the variability between different cancer types complicate the understanding of these pathways.
- Future Directions: Further research is needed to elucidate the precise mechanisms of PTMs in lipid metabolism and their roles in different cancer types. The integration of metabolomics and proteomics could provide deeper insights into the metabolic reprogramming in cancer and facilitate the development of targeted therapies.
Summary Table of Key Points
| Aspect | Details |
|---|---|
| Focus | Lipid metabolism reprogramming in cancer cells and TME |
| PTMs Discussed | Phosphorylation, acetylation, ubiquitination, SUMOylation, methylation |
| Key Enzymes | SREBP1, ACC, FASN, CD36, LDLR, PPARα |
| Therapeutic Implications | Targeting lipid metabolism and PTMs offers new avenues for cancer therapy |
| Research Gaps | Need for original experimental studies and exploration of PTMs across various cancer types |
This comprehensive overview highlights the intricate relationship between lipid metabolism and cancer, emphasizing the potential for therapeutic interventions targeting metabolic pathways.
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Literatures Citing This Work
- GDPD5 Related to Lipid Metabolism Is a Potential Prognostic Biomarker in Neuroblastoma. - Tengling Luo;Junwei Peng;Qijun Li;Yao Zhang;Yun Huang;Lei Xu;Genling Yang;Dongmei Tan;Qian Zhang;Yi Tan - International journal of molecular sciences (2022)
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation. - Jef Haerinck;Steven Goossens;Geert Berx - Nature reviews. Genetics (2023)
- Nanomaterials in tumor immunotherapy: new strategies and challenges. - Xudong Zhu;Shenglong Li - Molecular cancer (2023)
- DDIT4 Downregulation by siRNA Approach Increases the Activity of Proteins Regulating Fatty Acid Metabolism upon Aspirin Treatment in Human Breast Cancer Cells. - Aistė Savukaitytė;Agnė Bartnykaitė;Justina Bekampytė;Rasa Ugenskienė;Elona Juozaitytė - Current issues in molecular biology (2023)
- TRIM21-Promoted FSP1 Plasma Membrane Translocation Confers Ferroptosis Resistance in Human Cancers. - Jun Gong;Yuhui Liu;Wenjia Wang;Ruizhi He;Qilong Xia;Lin Chen;Chunle Zhao;Yang Gao;Yongkang Shi;Yu Bai;Yangwei Liao;Qi Zhang;Feng Zhu;Min Wang;Xu Li;Renyi Qin - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
- Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis. - Jian Chen;Deping Zhao;Yupeng Wang;Ming Liu;Yuan Zhang;Tingting Feng;Chao Xiao;Huan Song;Rui Miao;Li Xu;Hongwei Chen;Xiaoying Qiu;Yi Xu;Jingxuan Xu;Zelin Cui;Wei Wang;Yanchun Quan;Yifeng Zhu;Chen Huang;Song Guo Zheng;Jian-Yuan Zhao;Ting Zhu;Lianhui Sun;Guangjian Fan - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
- Recent progress in gene therapy for familial hypercholesterolemia treatment. - Yaxin Luo;Yaofeng Hou;Wenwen Zhao;Bei Yang - iScience (2024)
- Roles of posttranslational modifications in lipid metabolism and cancer progression. - Tianyu Feng;He Zhang;Yanjie Zhou;Yalan Zhu;Shiya Shi;Kai Li;Ping Lin;Jie Chen - Biomarker research (2024)
- Precise targeting of lipid metabolism in the era of immuno-oncology and the latest advances in nano-based drug delivery systems for cancer therapy. - Hongyan Zhang;Yujie Li;Jingyi Huang;Limei Shen;Yang Xiong - Acta pharmaceutica Sinica. B (2024)
- Drug Repurposing: A Conduit to Unravelling Metabolic Reprogramming for Cancer Treatment. - Shristy Chaudhary;Abhilash Rana;Seema Bhatnagar - Mini reviews in medicinal chemistry (2025)
... (8 more literatures)
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