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Pan-cancer perspectives on post-translational modifications and metastasis: Unraveling complex molecular mechanisms
Qilu Yan1, Shuya Jiang2, Wangzheqi Zhang2
1Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Abstract:
Metastasis is the leading cause of cancer death, due to complex molecular mechanisms. Post-translational modifications (PTMs) are essential in determining the function, structure, and interaction of proteins. Different steps of the metastatic cascade including the activation and rewiring of signaling pathways, epithelial to mesenchymal transition (EMT), cell migration and invasion, survival in the blood vessel, and colonization at a distance are modified by PTMs. Recent studies reveal that PTMs maintain the capacity of metastasis and phenotypic plasticity thus highlighting their essential role in metastasis biology. Even though the regulation mediated by PTMs is widely conserved, they are also tumor-type specific. Cancer metastasis is regulated by distinct patterns of enzymes and signaling pathways associated with PTMs, suggesting potential for diagnostic and therapeutic applications of PTM-based classification. In addition, widespread crosstalk between various classes of PTMs, whether cooperative or antagonistic, shapes regulatory networks that are multilayered and dynamic. The explanation of these regulatory mechanisms will enable the identification of critical control nodes, as well as provide a significant basis for developing PTM-informed anti-metastatic therapies.
Insights
Post-translational modifications (PTMs) are crucial for cancer metastasis, influencing key steps like cell migration and survival. Understanding PTMs offers new avenues for developing targeted anti-metastatic therapies.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Metastasis is the primary cause of cancer mortality, driven by intricate molecular processes.
- Post-translational modifications (PTMs) critically regulate protein function, structure, and interactions.
- PTMs are implicated in various stages of the metastatic cascade, including epithelial to mesenchymal transition (EMT) and cell invasion.
Purpose of the Study:
- To highlight the essential role of PTMs in metastasis biology and phenotypic plasticity.
- To explore the tumor-type specificity of PTM regulation in cancer metastasis.
- To underscore the potential of PTM-based classification for diagnostics and therapeutics.
Main Methods:
- Review of recent studies on PTMs in cancer metastasis.
- Analysis of signaling pathways and enzymes involved in PTM regulation.
- Investigation of PTM crosstalk and its impact on regulatory networks.
Main Results:
- PTMs are vital for maintaining metastatic capacity and phenotypic plasticity.
- PTM regulation is conserved but exhibits tumor-type specificity.
- Distinct PTM patterns are associated with cancer metastasis, suggesting diagnostic and therapeutic potential.
Conclusions:
- Understanding PTM regulatory mechanisms is key to identifying critical control nodes in metastasis.
- PTMs play a dynamic and multilayered role in shaping cancer cell behavior.
- PTM-informed strategies hold promise for developing novel anti-metastatic therapies.
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