Abstract
Cancer Stem-like Cells (CSCs) are a subpopulation of cancer cells with self-renewal capacity and are important for the initiation, progression and recurrence of cancer diseases. The metabolic profile of CSCs is consistent with their stem-like properties. Studies have indicated that enzymes, the main regulators of cellular metabolism, dictate functionalities of CSCs in both catalysis-dependent and catalysis-independent manners. This paper reviews diverse studies of metabolic enzymes, and describes the effects of these enzymes on metabolic adaptation, gene transcription and signal transduction, in CSCs.
Highlights
According to the hierarchical model, tumor is formed by a hierarchy of proliferative and progressively differentiated bulk of cells, which originated from a unique subpopulation of cells showing “stem-like” property, cancer stem-like cells (CSCs) [1]
This review focuses on the metabolic enzymes involved in carbohydrate, protein and lipid metabolism in CSCs, discussing their function in stemness promotion and the involved mechanisms
Lactic dehydrogenase (LDH)-A dedicates to the formation of chemoresistance of CSCs, as NHI can stimulate the releasing of deoxycytidine kinase, which can enhance the anti-tumor efficiency of Gemcitabine [24]
Summary
According to the hierarchical model, tumor is formed by a hierarchy of proliferative and progressively differentiated bulk of cells, which originated from a unique subpopulation of cells showing “stem-like” property, cancer stem-like cells (CSCs) [1]. A unique/ novel feature of CSCs is that they have the capacity to resist chemotherapy and irradiation due to expression of multidrug resistance related transporters and DNA repair mechanisms [2, 3] Together with their invasive and metastatic capabilities, CSCs correlate closely with tumor initiation, progression, and recurrence. In CSCs, many a metabolic enzyme shows both catalytic activities and transcriptional activities They induce and maintain the metabolic characteristics, and activate stem-like properties by transcriptional regulation or signal interaction (Figure 1). Such multiple layers of regulation carried out by metabolic enzymes indicate that these molecules can be used as potential targets for separation of CSCs, and detection and treatment of cancer diseases. This review focuses on the metabolic enzymes involved in carbohydrate, protein and lipid metabolism in CSCs, discussing their function in stemness promotion and the involved mechanisms
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