Cancer Cell Metabolism and Signaling

Cancer Cell Metabolism

• Cancer cells reprogram nutrient acquisition and metabolism to support their bioenergetic, biosynthetic, and redox demands.
• This reprogramming is a hallmark of cancer.
• Metabolic flexibility allows for diverse pathways to support these functions.
• Understanding metabolic reprogramming and its links to tumorigenesis and metastasis is crucial to developing new cancer treatments.

Multiple Ways to Disrupt Signaling Circuits

• Cancer cells can disrupt signaling pathways through various mechanisms, including changes in gene expression, affecting motility, proliferation, cytostasis, differentiation, and viability.

Why Deregulate Cellular Metabolism?

• Deregulating cellular metabolism is a key driver of many hallmark aspects of cancer, including maintaining rapid proliferative signaling, evading growth suppressors, avoiding immune destruction, enabling replicative immortality, tumor-promoting inflammation, activating invasion, and metastasis.
• These processes contribute to maintaining cancer cell viability and proliferation.

How Cells Harvest Energy

• Glucose oxidation occurs in stages:
  • Glycolysis
  • Pyruvate oxidation
  • Krebs cycle
  • Electron transport chain and chemiosmosis

Fate of Pyruvate

• In aerobic conditions, pyruvate is oxidized to acetyl-CoA, releasing CO2 and producing NADH.
• In anaerobic conditions, pyruvate is reduced to lactate or ethanol, regenerating NAD+ necessary for glycolysis to continue.

Cancer Cell Metabolism Details

• Many tumors reside in low-oxygen environments (hypoxia) and reprogram nutrient acquisition and metabolism to meet their needs.
• Cancer metabolism is a significant area of research in cancer biology, predating the discovery of oncogenes and tumor suppressor genes.

Nobel Prize Winners

• Otto Warburg (1931) - Warburg Effect
• William G. Kaelin Jr. (2019) - HIF1

Warburg Effect

• An increased glucose uptake and fermentation of glucose to lactate, even in the presence of functional mitochondria.
• This phenomenon is observed in many cancerous tumors and proliferating cells.

mTOR

• Mammalian target of rapamycin (mTOR) is a serine/threonine kinase crucial for cell proliferation, autophagy, and apoptosis.
• It acts through two main complexes, mTORC1 and mTORC2.
• mTOR activity is regulated by nutrients and is crucial for tumor cell survival.
• Cellular need for this factor is increased with low levels of nutrients.

Sterol Responsive Element Binding Protein (SREBP1)

• SREBP1 is a key regulator of lipid biosynthesis, including fatty acid synthesis.
• It plays a role in how rapidly cancer cells synthesize fatty acids.

Hypoxia-Inducible Factor 1 (HIF-1)

• HIF-1 plays a role in adapting to low-oxygen conditions.
• It changes how cancer cells metabolize glucose, allowing energy production to occur even without oxygen.

Oncogenes and Metabolism

• Oncogenes, such as Myc, drive the expression of genes that support anabolic growth, including those required for glycolysis and fatty acid synthesis.

Reactive Oxygen Species (ROS) and Redox Balance

• Cancer cells can have higher levels of ROS-scavenging enzymes compared to normal cells.
• These mechanisms prevent ROS-mediated cell death.

Future of Cancer Metabolism

• Modern technologies allow for the identification of thousands of metabolites in tissues, helping characterize metabolic changes in cancer, including how they may change based on therapy.
• Understanding how metabolism is affected by cancer development and progression can provide new targets and ideas for treatment strategies.

Explore the intricate mechanisms of cancer cell metabolism and signaling circuits in this quiz. Understand how metabolic reprogramming serves as a hallmark of cancer and its implications for tumorigenesis and treatment development. Test your knowledge on the disruption of cellular pathways and the significance of deregulated metabolism in cancer progression.