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Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer
Yu-Ting Tang1,2, Tian-Yi Chen1,2, Zi-Yi Liu1,2
1Department of Pharmacology and Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Abstract:
Cancer metastasis and drug resistance are intricately linked processes that drive cancer progression and poor prognosis. One of the hallmarks of cancer is metabolic reprogramming, which evolves at various stages of tumor metastasis and drug resistance progression. This reprogramming involves the dysregulation of metabolic enzymes, which not only regulate the metabolic status in cancer cells, but also play multifunctional roles through influencing downstream signaling networks, acting as protein kinases, post-translational modifications and multiple biological processes, thereby exacerbating cancer malignancy. This review focuses on the metabolic enzyme-associated protein-protein interactions (mPPIs) during tumor metastasis and therapeutic resistance, and discusses the roles of key enzymes in glycolysis, the serine synthesis pathway, the pentose phosphate pathway, the glucuronate pathway and the sorbitol pathway. Understanding the distinct multifunctionality of these metabolic enzymes is crucial for gaining valuable insights into cancer pathogenesis and identifying potential therapeutic vulnerability to combat metastatic progression and overcome therapy resistance.
Insights
Metabolic reprogramming in cancer involves enzyme changes that drive metastasis and drug resistance. Understanding these metabolic enzyme-associated protein-protein interactions (mPPIs) offers new therapeutic targets for combating cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer metastasis and drug resistance are critical challenges in oncology, significantly impacting patient prognosis.
- Metabolic reprogramming is a hallmark of cancer, evolving during tumor metastasis and therapy resistance.
- Metabolic enzymes not only regulate cellular metabolism but also possess multifunctional roles influencing signaling networks and biological processes.
Purpose of the Study:
- To review the role of metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer metastasis and drug resistance.
- To elucidate the multifunctional roles of key metabolic enzymes in various cancer pathways.
- To highlight the importance of understanding these interactions for developing novel therapeutic strategies.
Main Methods:
- Literature review focusing on metabolic enzyme-associated protein-protein interactions (mPPIs).
- Analysis of key enzymes involved in glycolysis, serine synthesis, pentose phosphate, glucuronate, and sorbitol pathways.
- Synthesis of information on the impact of mPPIs on cancer malignancy, metastasis, and drug resistance.
Main Results:
- Metabolic enzyme dysregulation and associated protein-protein interactions (mPPIs) are integral to cancer metastasis and drug resistance.
- Key enzymes in central metabolic pathways exhibit multifunctionality beyond basic metabolism, influencing cancer progression.
- Specific pathways like glycolysis and serine synthesis pathway are critical sites of metabolic enzyme involvement.
Conclusions:
- Understanding the complex mPPIs of metabolic enzymes is crucial for deciphering cancer pathogenesis.
- The multifunctionality of metabolic enzymes presents potential therapeutic vulnerabilities for targeting metastatic cancer and overcoming resistance.
- Targeting mPPIs offers a promising avenue for developing novel anti-cancer therapies against metastasis and drug resistance.
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