A study published in the journal Nature Communications showed that researchers have discovered a new Hippo signaling pathway inhibitor, which may provide new insights into how the key signaling pathway is shut down in cancer cells.
The key component member protein kinase Hippo
mutation can make tissue hyperplasia, and the phenotype in Drosophila looks like a hippo, so this signaling pathway is named Hippo signaling pathway.
The Hippo signaling pathway
controls the size and volume of organs in animals by regulating cell proliferation and apoptosis (or programmed death). Since cancer is caused by abnormal regulation and hyperproliferation of cells, the Hippo signaling pathway is of great significance in human cancer research.
Both development and cancer are closely related to cell proliferation and apoptosis. The imbalance of developmental pathways often leads to cancer, and the Hippo pathway is no exception. The Hippo signaling pathway is also known as the tumor suppressor pathway.
Silencing of the Hippo signaling pathway activates the downstream effectors Yap and Taz, which prompt tumor growth. Studies have confirmed that Hippo signaling is deregulated in many types of cancer, so cancer cells can proliferate and become more aggressive. However, we still know very little about how the Hippo pathway is dysregulated in cancer.
Through a focused RNAi screen, the researchers identified an STK25
enzyme, a serine/threonine kinase, as a regulator of Hippo's tumor suppressor pathway.
The researchers studied how STK25 regulates Hippo signaling by using multiple siRNA sequences targeting STK25. When STK25 was deleted in the cell line, they found that Hippo signaling was significantly impaired, consistent with what happened in the STK25 genetically deleted model.
Interestingly, bioinformatics analysis of TCGA indicated that STK25 was significantly deleted in a wide range of human cancers, suggesting that its loss can promote cancer formation.
Next, they assessed whether STK25 deletion status had an impact on the clinical course of the disease. They found that patients with sarcoma with STK25 deletion had a significantly shorter survival period, and the incidence of STK25 deletion was higher in patients with the recurrent disease than in patients without STK25 deficiency.
Taken together, the results of this study suggest that deletion of STK25 may be one of the mechanisms by which human cancers functionally inactivate Hippo signaling to promote tumorigenesis and disease progression. And the way STK25 regulates Hippo signaling is completely different from the way other existing molecules have been identified, which represents a completely new way in which major tumor suppressor pathways may be activated.
In the past, it is a challenge to learn about how some molecules involved in the cascade of the Hippo signaling pathway to start and shut down so that scientists can not make better use of its benefits in cancer research. Now, the researchers hope that their research will help to better understand the dysregulation of Hippo signaling in human cancers and to discover and develop new anticancer treatments from this signaling pathway.
CUSABIO team. Identification of STK25 kinase as an inhibitor of the Hippo signaling pathway. https://www.cusabio.com/c-20914.html