Linking CREB function with altered metabolism in murine fibroblast-based model cell lines.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Metabolism

Background:

• cAMP-responsive element binding protein (CREB) is overexpressed in various tumors, promoting cancer progression.
• Dysregulated CREB expression impacts cellular proliferation, migration, invasion, angiogenesis, and apoptosis.
• The relationship between CREB and cellular metabolism, particularly in HER-2/neu-transformed cells, requires further elucidation.

Purpose of the Study:

• To investigate the association between CREB expression/function and cellular metabolic alterations in HER-2/neu-transfected cells.
• To explore the impact of CREB modulation and hypoxia on cellular metabolism.
• To identify potential therapeutic targets within CREB-regulated metabolic pathways.

Main Methods:

• Comparative proteome-based analysis to identify metabolic protein expression changes.
• Assessment of glucose transporter 1 expression, glucose uptake, and glycolytic activity.
• Evaluation of intracellular and extracellular pH, lactate dehydrogenase, and lactate levels.
• Analysis of CREB phosphorylation, ERK, AKT, and reactive oxygen species (ROS) detoxification via catalase.

Main Results:

• CREB down-regulation in HER-2/neu cells altered metabolic protein expression, particularly in glycolysis.
• Reduced glucose transporter 1, glucose uptake, and glycolytic activity were observed upon CREB down-regulation.
• Hypoxia increased CREB activity, affecting cellular metabolism, pH, and lactate production.
• CREB phosphorylation correlated with altered ERK and AKT signaling, and CREB promoted ROS detoxification by catalase.

Conclusions:

• CREB function is intrinsically linked to altered cellular metabolism in HER-2/neu-transformed cells.
• Modulation of CREB affects key metabolic pathways, including glycolysis and pH regulation.
• Targeting CREB-associated metabolic alterations presents a promising therapeutic strategy for HER-2/neu-overexpressing cancers.