Metabolic Regulation: Cell Growth and Proliferation

Dear Colleagues,

Advancements in the last few decades have set a firm foundation for emergence of metabolism as a key cancer hallmark. It is not surprising to see metabolic regulations as fundamental mechanisms fostering additional energy and nutrient demands of the cancer cell. To support tumor growth and proliferation in an altered environment, a broader metabolic rewiring is necessary thus helping to acquire additional glucose and other nutrients including, amino acids, nucleotides, and lipids indispensable for the sustenance of cell growth. These metabolites fulfill energy demands and serve as substrates for biomass generation. Other factors that influence metabolic adaptations include specific cell types and the microenvironment. Interestingly, many of the metabolites also impact molecular signaling by regulating gene and protein expression. Further, they also influence the neighboring non-transformed cells in the vicinity of the tumor.

Cellular metabolism is highly complex and multifactorial making it extremely difficult to fully understand its regulation. However, state-of-the-art techniques like metabolic flux analysis are highly efficient in identifying and tracing the precise metabolites through metabolic pathways. Metabolic rewiring also causes changes in cellular bioenergetics which allows cancer cells to endure high proliferation rates. A deeper knowledge of cellular bioenergetics is advantageous for understanding of cancerous cell physiology. Measuring oxygen consumption rate (OCR) and extracellular acidification rate or rate of acid efflux (ECAR) are helpful in determining mitochondrial respiration and amount of lactic acid produced during glycolytic metabolism.

A deeper understanding of metabolic regulation has further sparked interest in identifying cancer-specific metabolic signatures that render more direct and substantial effects to encourage cancer cell proliferation and survival. The era of metabolomics has fueled the identification of pathways and metabolic markers that are causative in cancer generation and progression. Further, external factors like diet and exercise also directly influence metabolic regulation. Metabolomic, transcriptomic and proteomic profiling enables the identification of alterations associated with cancer and these approaches provide a complete picture of discrepancies observed in regulation at molecular and pathway levels. Targeting altered metabolic regulation to diminish tumor growth and energy reservoir is now a major focus of future research and could be more advantageous and effective in advanced cancer therapeutics. A better understanding of the principles of metabolic regulation may improve ways to treat different cancers but also other metabolic diseases that rely on such pathways.

Dr. Debabrata Banerjee
Dr. Deepshikha Mishra
Guest Editors

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