Alex Dean

Research Progress on Hippo Signaling Pathway

Blog Post created by Alex Dean on Jan 22, 2019

The Hippo pathway is a kinase chain consisting of a series of protein kinases and transcription factors. From lower animals to higher animals, the Hippo signaling pathway is highly conserved, and this signaling pathway plays an important role in all aspects of the body's cells.

[1] Nature: Blocking Hippo signaling pathway can reverse severe heart failure

In a new study, researchers from Baylor College of Medicine, the Texas Heart Institute, and the Shanghai Children's Medical Center in China found a previously unrecognized healing capacity of the heart. In a mouse model, they were able to reverse severe heart failure by silencing Hippo activity. The Hippo signaling pathway prevents myocardial regeneration. The relevant research results were published online in the Nature Journal on October 4, 2017, and the title of the paper is "Hippo pathway deficiency reverses systolic heart failure after infarction".

"The heart failure is still the leading cause of heart disease death,” said James Martin, MD, author of the paper, professor of regenerative medicine at Baylor College of Medicine and director of the Cardiovascular Cell Update Laboratory at the Texas Heart Institute. “The best treatment for this disease is to implant a ventricular assist device or a heart transplant, but the number of hearts available for transplantation is limited."

At the time of a heart attack, blood stops flowing into the heart, and some of the myocardium dies due to lack of oxygen. Myocardium does not regenerate; instead, dead heart tissue is replaced by scar tissue composed of fibroblasts, which is not conducive to heart pumping. The heart is functionally weakened. Most patients suffering from severe heart attacks develop heart failure.

[2] Major discoveries in the field of Hippo signaling pathway! Guan Kunliang's research group reports the important role of Hippo signaling pathway in tumor immune regulation in Cell
On December 1, 2017, the latest issue of Cell published an important article entitled "The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity" written by a research group of Professor Guan Kunliang of the University of California, San Diego, which is one of the most significant discoveries in the Hippo signaling pathway in the last two years. Prior to this study, researchers seemed to be unclear about the involvement of the Hippo signaling pathway in the regulation of tumor immunogenicity. Under the condition of knocking out LATS1/2, mice were able to induce enhanced anti-tumor immunity and inhibit tumorigenesis. For a long time, most studies have shown that the inactivation of Hippo signaling pathway can induce tumorigenesis in some organs, and LATS1/2 was also recognized as a tumor suppressor gene before, and in this article LATS1/2 exhibits "oncogene" properties that inhibit immunogenicity.

Tumor cells with poor immunogenicity will escape during host immunization and anti-epidemic. When LATS1/2 is knocked out in tumor, it can stimulate the secretion of extracellular vesicles enriched by nucleic acid, and then induce Toll-like receptor MYD88/TRIF. The type I interferon response stimulates multiple components of the host immune response to ultimately activate T cells. The activated T cells have the ability to assist tumor-specific cytotoxic T cell responses and B cell antibody production, ultimately destroying tumor formation.

[3] Onco Cancer Res: Research progress on Hippo Signaling Pathways, cancer and cell aging

Hpo/MST-Yki/YAP pathway plays an important role in regulating cell growth and organ size. YAP2 (Yes associated protein2) is the core protein of this pathway and participates in tumor development. Yuan Zengqiang Research Group of the Institute of Biophysics, Chinese Academy of Sciences, has been focusing on and studying the molecular regulation mechanism of YAP2 and its function in tumorigenesis and development. Recently, his research results were published in Oncogene and Cancer Research.

An article published online on Oncogene on April 1, 2013 reported the role of YAP2's novel molecular regulatory mechanisms in hepatoma cell proliferation and drug resistance. YAP2 has a variety of post-translational modifications (phosphorylation and ubiquitination) as proto-oncoproteins, regulating its transcriptional activity and function. The study revealed novel post-translational modifications of YAP2, acetylation and deacetylation, identifying SIRT1 as the major deacetylase of YAP2, enhancing the binding of YAP2 to the transcription factor TEAD4, promoting its transcriptional activity, and in anti-tumor drugs (CDDP). The treatment of YAP2 into the nucleus functions as a transcription factor, thereby enhancing the proliferation of liver cancer cells and resisting the resistance of tumor drugs. Correspondingly, the protein level of SIRT1 in liver cancer specimens was significantly higher than that in normal tissues, and it was positively correlated with the expression of CTGF in the downstream target gene of YAP2. These results provide a new basis for revealing the mechanism of liver cancer development and treatment.

[4] NCB: The new mechanism of Hippo signaling pathway is revealed
Researchers from the University of California, San Diego, Harvard University published an article entitled "YAP mediates crosstalk between the Hippo and PI (3) K-TOR pathways by suppressing PTEN via miR-29”, confirming that YAP inhibits PTEN via miR-29 and mediates the crosstalk between Hippo and PI(3)K-TOR signaling pathway. Related results were published in the November 11 issue of Nature Cell Biology.

The author of the article is Professor Guan Kunliang, who graduated from Hangzhou University in his early years. Professor Guan is mainly engaged in research on cell growth regulation, tumor biology and neurobiology signal transduction pathways. He has won a number of honors including the award "McArthur genius". He is currently a professor at the University of California, San Diego, and an adjunct professor and co-dean of the Institute of Life Sciences at Zhejiang University.

The Hippo signal transduction pathway is a signal transduction pathway discovered several years ago. The study found that the Hippo signaling pathway is a key signaling pathway involved in the regulation of organ size development. This view was first discovered in Drosophila. Later studies found that Hippo has the same function during mammalian development. In recent years, there is increasing evidence that this signaling pathway also regulates stem cell self-renewal and tissue regeneration, especially in relation to the occurrence of cancer. Therefore, the study of this pathway is not only an important topic of developmental biology, but also has guiding significance for the treatment of human diseases.


Author's Bio:

BOC Sciences is one of the fastest growing companies dedicated to a wide range of custom synthesis services in the pharmaceutical industry including nucleotide synthesis and nucleoside synthesis. In addition to supply of chemical products and services, this company also offers expertise in various signaling pathways, such as Apoptosis Signaling Pathway, Autophagy pathway, mTOR Signaling Pathway, RAS Signaling Pathway, B Cell Receptor Signaling Pathway, JNK Signaling Pathway, Erk Signaling Pathway, GPCR Signaling Pathway, etc.