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Metabolic Hallmarks of Metastasis Formation
Ilaria Elia1, Ginevra Doglioni1, Sarah-Maria Fendt1
1Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium.
Abstract:
Metastasis to distant organs is a predictor of poor prognosis. Therefore, it is of paramount importance to understand the mechanisms that impinge on the different steps of the metastatic cascade. Recent work has revealed that particular metabolic pathways are rewired in cancer cells to support their transition through the metastatic cascade, resulting in the formation of secondary tumors in distant organs. Indeed, metabolic rewiring induces signaling pathways during initial cancer invasion, circulating cancer cells depend on enhanced antioxidant defenses, and cancer cells colonizing a distant organ require increased ATP production. Moreover, the local environment of the metastatic niche dictates the metabolic pathways secondary tumors rely on. Here we describe mechanisms of metabolic rewiring associated with distinct steps of metastasis formation.
Insights
Cancer cells rewire metabolic pathways to spread to distant organs. Understanding these metabolic changes is crucial for improving prognosis and developing targeted therapies against metastasis.
Area of Science:
- Oncology
- Cancer Biology
- Metabolic Pathways
Background:
- Metastasis to distant organs significantly worsens patient prognosis.
- Understanding the metastatic cascade is critical for improving cancer outcomes.
- Metabolic pathways are increasingly recognized as key regulators of cancer progression.
Purpose of the Study:
- To elucidate the mechanisms of metabolic rewiring during distinct steps of the metastatic cascade.
- To highlight how metabolic adaptations support cancer cell invasion, circulation, and colonization.
- To underscore the role of the metastatic niche microenvironment in dictating metabolic dependencies.
Main Methods:
- Review of recent literature on cancer cell metabolism and metastasis.
- Analysis of metabolic adaptations required for invasion, survival in circulation, and organ colonization.
- Examination of the influence of the metastatic microenvironment on cancer cell metabolism.
Main Results:
- Metabolic rewiring supports cancer cell transition through the metastatic cascade.
- Specific metabolic pathways are essential for invasion, survival, and colonization.
- The metastatic niche environment imposes distinct metabolic demands on secondary tumors.
Conclusions:
- Metabolic reprogramming is a fundamental aspect of metastasis.
- Targeting cancer cell metabolism offers potential therapeutic strategies against metastatic disease.
- The interplay between cancer cell metabolism and the metastatic niche is a critical determinant of secondary tumor formation.
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