Novel Biological Pathway Could Offer new Treatment Option for Endometriosis

Targeting this pathway could offer a new treatment option against endometriosis in the future.

Key Points

Highlights:

• Researchers identify a new biological pathway that may be involved in endometriosis. 
  • Low oxygen levels downregulate the activity of a protein called LATS1 (Large Tumor Suppressor Kinase 1).
  • LATS1 blocks the activity of another protein called YAP1, which is involved in cell proliferation. 
  • In the endometriosis environment where oxygen levels are low, such as the peritoneum, the block on YAP1 is lifted, making it overactive and resulting in excessive growth of endometriosis tissues.
• Targeting this pathway could be a new approach to treating endometriosis in the future.

Importance:

• Ectopic endometriosis tissues success to survive in the microenvironment where oxygen levels are low which should be accomplished by regulating the expression of a subset of genes.
• Previous research informed that the level of Hypoxia-inducible factor-1α (HIF-1α) is elevated in endometriotic tissue reflecting that ectopic endometriotic cells are under hypoxic stress.
• However, the master regulator controlling these genes remains to be characterized.

What’s done here?

• The researchers used bioinformatics tools and a mouse model to explain how endometriosis tissue can grow outside the uterus where there is very little oxygen and where endometriotic tissue should not normally be able to grow.
• The researchers showed that blocking the activity of YAP1 resulted in processes involved in the development of endometriosis such as the formation of steroid hormones, new blood vessels, nerve cells, as well as inflammation; cell migration and proliferation to be abolished. 
• Using a mouse model they showed that blocking the activity of YAP1 reduced endometriosis but did not have an adverse impact on the fertility of the animals or the growth rate of their offspring.

Key results:

• Blocking the activity of a protein called YAP1, can reduce biological events associated with endometriosis without negatively affecting fertility.

Limitations of this study:

• It is not known whether blocking the activity of YAP1 can prevent the development of endometriosis.  

Lay Summary

Researchers have identified a novel biological pathway that may be involved in endometriosis. Targeting this pathway may, therefore, be a new alternative approach to treating the condition in the future. 

Endometriosis is characterized by the tissue that normally lines the walls of the uterus to grow in the peritoneum, or space lining the inside of the abdomen causing pain and even infertility. However, there is very little oxygen in this area, and therefore it is usually not an environment that is suitable for endometriotic tissue to grow. Scientists think that lesions that are formed in endometriosis express a set of genes that allow them to survive in this environment low in oxygen. 

To identify which biological pathway regulates the expression of these genes, a team of researchers at National Cheng Kung University in Taiwan used bioinformatics tools and validated their findings in a mouse model. 

According to the team, low levels of oxygen downregulate the activity of a protein called LATS1, which normally blocks the activity of another protein called YAP1 that is involved in cell proliferation. So in an environment where oxygen levels are low, such as the peritoneum, the block on YAP1 is lifted, making it overactive. The result is excessive cell proliferation or growth of endometriotic tissue. 

The researchers showed that blocking the activity of YAP1 resulted in biological processes involved in the development of endometriosis such as the formation of steroid hormones, new blood vessels, and nerve cells, as well as inflammation, and cell migration and proliferation to be abolished. 

Importantly, the researchers showed using a mouse model that blocking the activity of YAP1 reduced endometriosis but did not have an adverse impact on the fertility of the animals or the growth rate of their offspring. 

They concluded that targeting the hypoxia/LATS1/YAP1 pathway could be a new option in the future to treat women with endometriosis without affecting their fertility. 

The study was published in the Journal of Pathology. 

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28608501