Abstract
Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redox balance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acid synthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations in peroxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linked to metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-related disorders, revealing the significance of peroxisome metabolism in human health. Cancer is a disease with metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functional effects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles, such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated than it is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomes and the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential of inactivating peroxisomes to target cancer metabolism, which may pave the way for more effective cancer treatment.
Highlights
Metabolic reprogramming is a hallmark of cancer and contributes to a selective advantage for the initiation and progression of malignant cells [1]
Some cancer cells rely on peroxisomal lipid breakdown for energy supply
Peroxisomal lipid synthesis and redox balance can support the survival of cancer cells in the tumor microenvironment, where nutrients and oxygen are frequently scarce
Summary
Metabolic reprogramming is a hallmark of cancer and contributes to a selective advantage for the initiation and progression of malignant cells [1]. The enzymes include metabolic proteins critical for lipid metabolism, such as ether phospholipid synthesis, very long and branched chain fatty acid oxidation, and hydrogen peroxide (H2 O2 ) metabolism [4]. Lipid metabolism has emerged as critical for tumorigenicity [6] Lipid synthesis pathways, such as lipogenesis-producing triglycerides and phospholipids and cholesterol synthesis, are essential for cell membrane structure, energy storage, and cell signaling mediation [7]. Some tumor types, such as prostate cancer and hematological malignancy, exhibit increased dependence on fatty acid oxidation for their tumorigenic growth [9,11]. Targeting multiple metabolic pathways may be a more potent strategy for treating cancer In this regard, a better understanding of the less recognized aspect of cancer metabolism may facilitate the development of more effective and selective cancer treatments. I discuss the anticancer effect of peroxisomal function inhibition that might be exploited for improved cancer therapy
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