Metabolic reprogramming in cervical cancer and metabolomics perspectives

Abstract

Cumulative studies have shown that metabolic reprogramming is a hallmark of malignant tumors. The emergence of technological advances, such as omics studies, has strongly contributed to the knowledge of cancer metabolism. Cervical cancer is among the most common cancers in women worldwide. Because cervical cancer is a virus-associated cancer and can exist in a precancerous state for years, investigations targeting the metabolic phenotypes of cervical cancer will enhance our understanding of the interference of viruses on host cells and the progression of cervical carcinogenesis. The purpose of this review was to illustrate metabolic perturbations in cervical cancer, the role that human papillomavirus (HPV) plays in remodeling cervical cell metabolism and recent approaches toward application of metabolomics in cervical disease research. Cervical cancer displays typical cancer metabolic profiles, including glycolytic switching, high lactate levels, lipid accumulation and abnormal kynurenine/tryptophan levels. HPV, at least in part, contributes to these alterations. Furthermore, emerging metabolomics data provide global information on the metabolic traits of cervical diseases and may aid in the discovery of biomarkers for diagnosis and therapy.

Keywords: Cervical cancer; HPV; Metabolomics; Warburg effect; p53.

Fig. 1

Metabolic regulation in cancer and cervical cancer. A Various cancers share several metabolic features in common. Here, we briefly illustrate typical characteristics of cancer metabolism. Generally, the uptake of glucose, amino acids and FAs is increased. Glycolysis is the leading energy source and consequently increases lactate production. Intermediates of glycolysis and glutamine metabolism are used for various biosynthesis pathways. De novo synthesis of FA is increased, and the generated FAs are further utilized in signal transduction, cellular component constitution and FAO. B Glycolysis, FA metabolism and amino acid metabolism are the most affected pathways in cervical cancer. The enzymes and transporters in the figure are all enhanced in cervical cancer or positively related to tumor aggressiveness. The figure was generated using PathVisio 3.0.0+ [102]