Cell Metabolism

mTOR Regulates Cell Metabolism

Cells have a complex sensing system designed to ensure that they do not undergo periods of growth unless adequate levels of nutrients are available to produce the energy necessary to support that growth. The rapidly expanding field of study dedicated to understanding how living systems obtain and utilize energy is known as bioenergetics.

Bioenergetic research has shown that mTOR plays a key role in regulating cell metabolism.^1-3 When adequate levels of nutrients (glucose, amino acids, lipoproteins, minerals) are available, mTOR is activated and turns on the cell's translational machinery, which includes the ribosomes and is responsible for the synthesis of proteins that are essential for cell growth and other cellular functions.¹

Among the key metabolism-related proteins whose production is upregulated when mTOR is active are:

• Nutrient transporter proteins found on the cell surface; an increase in these proteins results in greater uptake of amino acids and other nutrients by the cell¹
• HIF1-α, a key subunit of hypoxia-inducible factor (HIF), a master transcription factor that regulates the expression of a number of genes that code for proteins involved in angiogenesis as well as cell metabolism, proliferation, motility, adhesion, and survival³

Conversely, when nutrient levels are inadequate, mTOR is inactivated, protein synthesis is inhibited, and cell growth is arrested.¹

The role of mTOR in cell metabolism.

In many cancers, mTOR is inappropriately "switched on" due to the abnormal activation of one or more of the upstream signaling pathways that regulate mTOR activity. As a result, mTOR's ability to inhibit protein synthesis and cause growth arrest when nutrients are scarce becomes compromised.³

Cancer cells have nutrient requirements that are both greater and different than those of normal cells. For example, many types of cancer cells rely on glycolysis, rather than oxidative phosphorylation, for the majority of their energy needs—even when oxygen is present. Consequently, their need for glucose is significantly greater than that of normal cells.⁴

Abnormally activated mTOR may give cancer cells a competitive growth advantage by:

• Increasing angiogenesis, which increases the number of blood vessels through which nutrients can reach the cell^1,3
• Increasing production of nutrient transporter proteins; this increases the cell's ability to import essential nutrients^1,3
• Increasing production of the core enzymes necessary for glycolysis, which enables cancer cells to survive and grow under hypoxic conditions³

Increased glucose uptake and glycolysis has been shown to correlate with poor prognosis and increased invasiveness and metastatic potential in a number of tumor types.⁴