METABOLOMICS AND CELL SIGNALING IN CANCER PROGRESSION

Abstract

 Signalling-cellular metabolism interplay has a large role in cancer growth.  In this study, the researchers investigate these relationships using high-resolution metabolomics and quantitative signaling analysis to determine how to figure out the molecular basis of tumour growth.  A multi-dimensional approach to the description of the most suitable modes of action of cancer drugs was performed by examining samples of cancer tissue and cell cultures representing nine experimental groups in a mixed-method approach to an experiment combining the method of UPLC-MS/MS-based profiling and in vitro kinase tests.  The findings indicated that the concentration of lactate and glutamine increased progressively, whereas the level of AMPK activity decreased steadily and mTOR level increased dramatically. It indicates that their cells were reprogramming metabolically and in signalling in a co-ordinated way which is characteristic of cancer.  Scatter and correlation analyses were used and demonstrated great positive correlations between the concentration of important metabolites and pro-growth indicators of signalling.  Hybrid visualisation plots indicated that metabolic-signaling axis became stronger as the disease progressed.  The majority of the samples (over 65 percent) reported high mTOR activity, the indicator of anabolic growth and reduced response to energy stress.  Computer network modelling was used to validate the results and make sure that they were biologically meaningful with regard to expert opinion.  This combination in effect does not only make the complex biochemical layering of the cancer development more explainable, but also demonstrates potential co-targeting methods through the application of metabolic inhibitors and signalling modifiers.  The research in general contributes to our understanding of the science of cancer system biology and demonstrates the potential usefulness of multi-dimensional profiling in identification of therapeutic targets which can be tackled.