Analysis of the role of the Hippo pathway in cancer

Abstract

Cancer is a serious health issue in the world due to a large body of cancer-related human deaths, and there is no current treatment available to efficiently treat the disease as the tumor is often diagnosed at a serious stage. Moreover, Cancer cells are often resistant to chemotherapy, radiotherapy, and molecular-targeted therapy. Upon further knowledge of mechanisms of tumorigenesis, aggressiveness, metastasis, and resistance to treatments, it is necessary to detect the disease at an earlier stage and for a better response to therapy. The hippo pathway possesses the unique capacity to lead to tumorigenesis. Mutations and altered expression of its core components (MST1/2, LATS1/2, YAP and TAZ) promote the migration, invasion, malignancy of cancer cells. The biological significance and deregulation of it have received a large body of interests in the past few years. Further understanding of hippo pathway will be responsible for cancer treatment. In this review, we try to discover the function of hippo pathway in different diversity of cancers, and discuss how Hippo pathway contributes to other cellular signaling pathways. Also, we try to describe how microRNAs, circRNAs, and ZNFs regulate hippo pathway in the process of cancer. It is necessary to find new therapy strategies for cancer.

Keywords: Cancer; Hippo pathway; YAP/TAZ.

Fig. 1

Hippo pathway Phosphorylated MOB recruits LATS (together with SAV and MST1/2). LATS is then phosphorylated by hippo to generate activated LATS, which can then phosphorylate YAP/TAZ and promote their cytoplasmic localization by creating a binding site for 14-3-3 proteins. YAP/TAZ and TEAD, the heterodimer, can enhance cancer

Fig. 2

YAP protein and TAZ protein YAP protein is involved in YAP1 and YAP2 proteins. YAP1, it is involved in one WW domain, whereas, YAP2 composes of two WW domains. TAZ isoform that is commonly studied possesses one WW domain. In contrast with YAP, TAZ lacks of p-rich and SH3-binding domains

Fig. 3

Different pathways regulation of hippo pathway. Wnt pathway and AMPK pathway inhibit YAP protein. TAZ protein promotes TGF-β pathway. KRAS and MAPK/ERK promotes YAP protein

Fig. 4

miRNAs and Hippo pathway. YAP/TAZ could inhibit the processing of pri-miRNA to pre-miRNA. Several miRNAs can make an effect on Hippo pathway

Fig. 5

The relationship between zinc finger proteins and hippo pathway in cancers. MZF1 promote osteosarcomas through stimulation of YAP1 expression. ZFP226 was able to induce apoptosis by activating hippo signaling in human breast adenocarcinoma. Cooperation of ZEB1 and YAP stimulates and increases risk in breast cancer. CIZ1 interacted with the transcriptional factor YAP in hepatocellular carcinoma and enhanced cancer growth

Fig. 6

Hippo pathway-targeted inhibitors. Current Hippo pathway-targeted drugs have been discussed in the review, as shown in the figure