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The role of the Hippo-YAP pathway in Tumorigenesis

Ploeg, E.R. van der (2014) The role of the Hippo-YAP pathway in Tumorigenesis. Bachelor's Thesis, Biology.

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In this essay an overview is shown of the function of Yes Associated Protein (YAP) in the Hippo pathway and its role in tumorigenesis. The Hippo pathway has been described as an important regulator of cell growth. The pathway takes its name form one of its key signaling components, the protein kinase Hippo (Hpo). Mutations in this gene leads to tissue overgrowth or a hippopotamus-like phenotype in the D. Melanogaster. The Hippo pathway is highly conserved throughout the evolution. The hippo pathway and its effector, YAP, have emerged as important regulators of organ size and proliferation. Amplification of YAP has been found in multiple different tumors types and causes multiple oncogenic properties in cell lines. YAP overexpression stimulates proliferation and increases anti-apoptotic signals, increased levels of YAP can also can induce epithelial to mesenchymal transition (EMT). Paradoxically YAP is not only described as potent oncogene but also as tumor suppressor gene, in some tumors YAP is down regulated. Down regulated YAP results in suppressed anoikis, increased migration and invasiveness. When YAP is amplified it also has an important clinical relevance since high levels of YAP are associated with poor overall survival in patients with ovarian cancer and Hepatocellular carcinomas. YAP can also serve as potential direct or indirect target for anti-tumoral effect. When YAP is amplified microRNA-375 can directly target YAP and causes a decrease in proliferation and migration. γ-secretase inhibitors causes also decreased proliferation and migration by targeting Notch which is activated by YAP. Also when YAP is down regulated inhibition of Macrophage Stimulating 1 (MST1) leads to restoration of YAP levels and causes more apoptosis and a decreased organ size. This overview stresses the importance of the Hippo-YAP pathway in tumorigenesis.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:57
Last Modified: 15 Feb 2018 07:57

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