Disease Mechanism

Figure 2. from the Meller et al. paper. This shows a connection fatty acid oxidation has on other metabolic products.


The mechanism involving prostate cancer and metabolism is currently being studied. Previously, studies did not analyze the connection between metabolism and prostate cancer but within the last five years more studies have published about this association. The Meller et al. group was the first group to tie the Erg fusion mutation in pancreatic cancer into metabolism issues. It was found that the dysregulation of Erg can lead into the improper metabolism of fatty acids. Furthermore, other metabolism issues allow the pancreatic cancer cells to store energy which it uses to rapidly go through the cell cycle. In addition to the cells hijacking the metabolism systems put in place to create energy, the prostate cancer cells also have multiple workarounds to accelerate growth.

The Yu et al. group looked at the TMPRSS2-ERG Mutation and connected it with the progression of prostate cancer. Through experiments, the Yu et al. group was able to identify the TMPRSS2-ERG mutation playes a very significant role in the growth of cancer cells. Before this paper, the TMPRSS2-ERG mutation was thought to be only a random mutation but the Yu et al. group found that the mutation has a role in disrupting androgen receptors, common receptors found in the prostate gland. It was found that the mutation downregulated the android receptors by binding to inhibiting AR activity at the AR gene location. This causes a repressive epigenetic effect through the activation of methyltransferases and Polycomb group proteins. These epigenetic affects allow the cancer cell to grow and multiply in their location.

While the TMPRSS2-ERG mutation has recently been linked to growth, it has also been linked to the metastasis of prostate cancer, specifically, metastasis into the bones. The Deplus et al. group reported in 2017 that the TMPRSS2-ERG mutation has been linked to metastasis into the bones. The TMPRSSS2-ERG mutation achieves this through sophisticated mechnism. First, the tumor mass grows. After this is completed, the cancer cells spread to the bone tissue through a mechanism that still needs explored. Once arrived at the bone tissue, the TMPRSS2-ERG mutated cancer cells deregulate gene controlling cell migration, cell adhesion, and skeletal physiology. Lastly, the cancer cells disrupt the metabolism of the bone cells to funnel resources into rapid growth. While there has been a lot of work done in the recent decade to understand the underpinnings of how this mutation causes and spreads cancer mechanistically, there is still many areas left unexplored.

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