Abstract
Mitochondrial pyruvate carrier 1 (MPC1) is a key metabolic protein that regulates the transport of pyruvate into the mitochondrial inner membrane. MPC1 deficiency may cause metabolic reprogramming. However, whether and how MPC1 controls mitochondrial oxidative capacity in cancer are still relatively unknown. MPC1 deficiency was recently found to be strongly associated with various diseases and cancer hallmarks. We utilized online databases and uncovered that MPC1 expression is lower in many cancer tissues than in adjacent normal tissues. In addition, MPC1 expression was found to be substantially altered in five cancer types: breast-invasive carcinoma (BRCA), kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and prostate adenocarcinoma (PRAD). However, in KIRC, LUAD, PAAD, and PRAD, high MPC1 expression is closely associated with favourable prognosis. Low MPC1 expression in BRCA is significantly associated with shorter overall survival time. MPC1 expression shows strong positive and negative correlations with immune cell infiltration in thymoma (THYM) and thyroid carcinoma (THCA). Furthermore, we have comprehensively summarized the current literature regarding the metabolic reprogramming effects of MPC1 in various cancers. As shown in the literature, MPC1 expression is significantly decreased in cancer tissue and associated with poor prognosis. We discuss the potential metabolism-altering effects of MPC1 in cancer, including decreased pyruvate transport ability; impaired pyruvate-driven oxidative phosphorylation (OXPHOS); and increased lactate production, glucose consumption, and glycolytic capacity, and the underlying mechanisms. These activities facilitate tumour progression, migration, and invasion. MPC1 is a novel cancer biomarker and potentially powerful therapeutic target for cancer diagnosis and treatment. Further studies aimed at slowing cancer progression are in progress.
Highlights
Mitochondria are involved in bioenergetic, biosynthetic, and signalling organelle functions [1]
We explored the correlation between Mitochondrial pyruvate carrier 1 (MPC1) expression and patient prognosis
The results indicated that MPC1 was significantly differentially expressed in many cancers, such as breast-invasive carcinoma (BRCA), kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and prostate adenocarcinoma (PRAD)
Summary
Mitochondria are involved in bioenergetic, biosynthetic, and signalling organelle functions [1]. Mitochondria function as energy factories for cells and are essential. Metabolic reprogramming helps provide ATP and essential macromolecules for protein and nucleotide biosynthesis in cancer cells [12–15]. Cancer cells undergo metabolic reprogramming that enhances metabolic plasticity, enables the tumour to survive in a nutrient-scarce environment [16], and facilitates survival, proliferation, and metastasis [7, 17, 18]. Tumour cells typically display several, but not necessarily all, hallmarks of cancer, such as decreased glucose uptake, opportunistic nutrient acquisition, glycolysis, increased nitrogen assimilation, aberrant regulation of metabolically driven genes, and increased lactate production [7, 19, 20]. Known as the Warburg effect [13], is one of the earliest altered metabolism phenotypes seen in tumour cells [21, 22]. Aerobic glycolysis end products such as lactate may contribute to microenvironment alterations and facilitate tumorigenesis and cancer progression [22, 24, 25]
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