An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression
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View abstract on PubMed
Summary
This summary is machine-generated.Endosomal pH regulator NHE9 suppresses cyclic AMP (cAMP) levels in colorectal cancer cells. This promotes a hybrid epithelial-mesenchymal state, driving tumor invasion and poor prognosis.
Area Of Science
- Oncology
- Cell Biology
- Molecular Biology
Background
- Suppressed cyclic AMP (cAMP) levels are linked to cancer, but the underlying molecular mechanisms are unclear.
- Endosomal pH is a potential regulator of cellular processes, including cAMP homeostasis.
Purpose Of The Study
- To investigate the role of endosomal pH in regulating cytosolic cAMP levels.
- To identify molecular players involved in cAMP homeostasis and their connection to colorectal cancer progression.
Main Methods
- Experimental studies combining cell biology techniques.
- Computational analysis to understand molecular interactions.
- In vitro and in vivo assays to assess tumor growth and invasion.
Main Results
- The Na+/H+ exchanger NHE9 was identified as a key regulator of endosomal pH.
- NHE9 activity leads to endosomal alkalinization, which increases cytosolic calcium and represses cAMP levels.
- Higher NHE9 expression correlates with a hybrid epithelial-mesenchymal (E/M) phenotype, poor prognosis, and increased invasiveness in colorectal cancer.
Conclusions
- NHE9-mediated endosomal alkalinization and subsequent cAMP suppression create a pseudostarvation-induced invasion state in colorectal cancer.
- NHE9 represents a potential therapeutic vulnerability for targeting colorectal cancer progression and metastasis.
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