The Hippo Signaling Pathway in Development and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (15 February 2021) | Viewed by 8617

Special Issue Editor


E-Mail Website1 Website2
Guest Editor
The Francis Crick Institute, London, UK
Australian National University, Canberra, Australia
Interests: Hippo signaling in Drosophila and mammals

Special Issue Information

Dear Colleagues,

The Hippo pathway acts via two key transcriptional co-activators YAP (or YAP1) and TAZ (or WWTR1), that are frequently activated during the growth and progression of many solid tumours, including lung, colorectal, breast, pancreatic and liver carcinomas, as well as melanoma and glioma. YAP/TAZ bind to TEAD-family co-activators to drive cancer cell survival, proliferation, invasive migration and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP-TEAD cooperates with the RAS-induced AP-1 (FOS/JUN) transcription factor to drive tumour growth and cooperates with MRTF-SRF to promote the activation of cancer-associated fibroblasts, matrix stiffening and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2-LATS1/2) pathway and the key upstream activators are mechanically-induced Integrin-SRC and E-cadherin-AJUBA/TRIP6/LIMD1, growth factor-induced PI3K-AKT and inflammation-induced G-protein coupled receptor (GPCR) signals, all of which antagonise the Hippo pathway. Strategies to target YAP/TAZ activity in cancer are being developed that may offer prospects for synergy with established pillars of cancer therapy. This field is progressing rapidly and a Special Issue on the role of this pathway in normal development and cancer is timely.

Dr. Barry Thompson
Guest Editor

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Keywords

  • Hippo
  • YAP
  • TAZ
  • development
  • regeneration
  • cancer
  • metastasis

Published Papers (2 papers)

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Research

13 pages, 2510 KiB  
Article
Upregulation of CD109 Promotes the Epithelial-to-Mesenchymal Transition and Stemness Properties of Lung Adenocarcinomas via Activation of the Hippo-YAP Signaling
by Kang-Yun Lee, Tai-Chih Kuo, Chih-Ming Chou, Wen-Jing Hsu, Wei-Cheng Lee, Jia-Zih Dai, Sheng-Ming Wu and Cheng-Wei Lin
Cells 2021, 10(1), 28; https://doi.org/10.3390/cells10010028 - 25 Dec 2020
Cited by 18 | Viewed by 3596
Abstract
Metastasis is the leading cause of death in lung adenocarcinomas. Identifying potential prognostic biomarkers and exploiting regulatory mechanisms could improve the diagnosis and treatment of lung cancer patients. We previously found that cluster of differentiation 109 (CD109) was upregulated in lung tumor tissues, [...] Read more.
Metastasis is the leading cause of death in lung adenocarcinomas. Identifying potential prognostic biomarkers and exploiting regulatory mechanisms could improve the diagnosis and treatment of lung cancer patients. We previously found that cluster of differentiation 109 (CD109) was upregulated in lung tumor tissues, and CD109 overexpression was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. However, the contribution of CD109 to lung tumorigenesis remains to be elucidated. In the present study, we identified that CD109 was upregulated in metastatic lung adenocarcinoma cells, and elevation of CD109 was correlated with epithelial-to-mesenchymal transition (EMT) traits in patients with lung adenocarcinoma. Functionally, CD109 expression was crucial for EMT gene expressions, tumor invasiveness, and cancer stemness properties. Moreover, elevation of CD109 was accompanied by upregulation of the yes-associated protein (YAP) signature in metastatic lung cancer cells and lung cancer patients, and activation of YAP was demonstrated to participate in CD109-elicited EMT gene expressions and tumor invasiveness. Our study reveals the molecular mechanism underlying CD109 in lung tumor aggressiveness, and CD109 could be a potential diagnostic and therapeutic target for lung cancer patients. Full article
(This article belongs to the Special Issue The Hippo Signaling Pathway in Development and Disease)
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24 pages, 5609 KiB  
Article
The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation
by Sepideh Fallah and Jean-François Beaulieu
Cells 2020, 9(8), 1895; https://doi.org/10.3390/cells9081895 - 13 Aug 2020
Cited by 12 | Viewed by 4442
Abstract
The human intestine is covered by epithelium, which is continuously replaced by new cells provided by stem cells located at the bottom of the glands. The maintenance of intestinal stem cells is supported by a niche which is composed of several signaling proteins [...] Read more.
The human intestine is covered by epithelium, which is continuously replaced by new cells provided by stem cells located at the bottom of the glands. The maintenance of intestinal stem cells is supported by a niche which is composed of several signaling proteins including the Hippo pathway effectors YAP1/TAZ. The role of YAP1/TAZ in cell proliferation and regeneration is well documented but their involvement on the differentiation of intestinal epithelial cells is unclear. In the present study, the role of YAP1/TAZ on the differentiation of intestinal epithelial cells was investigated using the HT29 cell line, the only multipotent intestinal cell line available, with a combination of knockdown approaches. The expression of intestinal differentiation cell markers was tested by qPCR, Western blot, indirect immunofluorescence and electron microscopy analyses. The results show that TAZ is not expressed while the abolition of YAP1 expression led to a sharp increase in goblet and absorptive cell differentiation and reduction of some stem cell markers. Further studies using double knockdown experiments revealed that most of these effects resulting from YAP1 abolition are mediated by CDX2, a key intestinal cell transcription factor. In conclusion, our results indicate that YAP1/TAZ negatively regulate the differentiation of intestinal epithelial cells through the inhibition of CDX2 expression. Full article
(This article belongs to the Special Issue The Hippo Signaling Pathway in Development and Disease)
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