PI3K Pathway

This cartoon of the PI3K pathway puts it in reference to other pathways. Additionally, it demonstrates that the PI3K pathway can impact metabolism and proliferation.

Recent literature has demonstrated that the TMPRSS2-ERG mutation is connected to the phosphoinositide 3 kinase (PI3K) pathway. The PI3K pathway is responsible for catalyzing the production of hosphatidylinositol-3,4,5-trisphosphate – a key component to cell survival, gene regulation, cell metabolism, and cytoskeletal rearrangements. Since there are many roles the PI3K pathway, many different phosphoinositide 3 kinase are present in eukaryote cells. These different kinases have different targets associated with the different signals the PI3K pathway uses to regulate the aforementioned functions. One important function that is PI3K pathway plays a role in regulating AKT (Cantley et al.).

Research in the past two decades has looked at what pathways the TMPRSS2-ERG mutation works through. Researchers found that the PI3K pathway is used to activate another pathway AKT. Since AKT helps regulate processes similar to the PI3K pathway through phosphorylation, it is important to ensure that this protein is properly regulated as well (Zong et al).

The regulation of the AKT pathway is important to ensure that cells proliferate is function at the appropriate rate. Through recent experiments from the Brunet et al. group we are able to confirm that the AKT pathway can block cellular death by two paths. The first way is to stop the machinery such as APAF1 from signaling the death of the cell. The second way to stop cell death is to adjust the regulation of genes signaling for cellular death. This fine balance between life and death is very important for prostate cancer cells that exhibit the TMPRSS2-ERG mutation. Often, the prostate cancer cells take advantage of these mechanism and exploit them. This exploitation allows the prostate cancer cells to stop them from dying. In addition to preventing death, the prostate cancer cells are able to change the flux of metabolic products and sources to grow rapidly by taking advantage of these pathways. This ties into the biochemical mechanism behind prostate cancer.

1 Comment

  1. Hi Calvin, I enjoyed reading your post! Do you know if the TMPRSS2-ERG mutation and the making of phosphatidylinositol-3,4,5-trisphosphate is involved in other cancers, besides prostate cancer? It makes me think back to the talk we went to at LVHN where it was mentioned that cancers are commonly treated by the type of cancer they are rather than treating the mutation. Is prostate cancer currently treated as prostate cancer or as the TMPRSS2-ERG mutation?

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