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Hippo pathway signaling and YAP/TAZ
Research Guide
What is Hippo pathway signaling and YAP/TAZ?
Hippo pathway signaling is an evolutionarily conserved cascade that controls organ size, tissue growth, and cell proliferation through regulation of the transcriptional co-activators YAP and TAZ.
The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It controls numerous biological processes, including cell growth, fate decisions, and organ size control. There are 27,835 works on Hippo pathway signaling and YAP/TAZ in cell biology.
Topic Hierarchy
Research Sub-Topics
YAP/TAZ Mechanotransduction
This sub-topic explores how YAP/TAZ sense and transduce mechanical cues from ECM stiffness, cell density, and cytoskeleton into transcriptional outputs. Researchers study nuclear shuttling, actin linkages, and focal adhesion roles.
Hippo Pathway in Cancer
This sub-topic investigates Hippo-YAP/TAZ dysregulation in tumorigenesis, metastasis, therapeutic targeting, and tumor microenvironment interactions. Researchers analyze mutations in MST1/2, LATS1/2, and clinical correlations.
Hippo Pathway Organ Size Control
This sub-topic examines feedback mechanisms, tissue growth termination, and inter-organ coordination via Hippo effectors. Researchers use Drosophila and mouse models to dissect proliferation-quiescence balance.
Hippo-YAP/TAZ in Stem Cells
This sub-topic covers YAP/TAZ roles in stem cell self-renewal, differentiation, pluripotency maintenance, and lineage specification. Researchers study iPSCs, tissue-specific progenitors, and regeneration contexts.
Hippo Pathway Core Kinase Cascade
This sub-topic details upstream activators (MST1/2-SAV1, LATS1/2-MOB1), phosphorylation dynamics, and scaffold regulation of the canonical Hippo cascade. Researchers elucidate signal integration and feedback loops.
Why It Matters
Hippo pathway signaling and YAP/TAZ regulate mechanotransduction, cell proliferation, tissue growth, organ size, cancer progression, and stem cell regulation. "Role of YAP/TAZ in mechanotransduction" by Dupont et al. (2011) demonstrated that YAP/TAZ activity responds to mechanical cues from the extracellular matrix and cell density, linking physical forces to gene expression changes that drive cell proliferation and tissue homeostasis. Dysregulation contributes to tumor progression, as explored in connections to "Epithelial–mesenchymal transitions in tumour progression" by Thiery (2002) with 6630 citations and "Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment" by Hanahan and Coussens (2012) with 4566 citations.
Reading Guide
Where to Start
"Role of YAP/TAZ in mechanotransduction" by Dupont et al. (2011) is the first paper to read, as it provides a foundational explanation of YAP/TAZ integration of mechanical signals into Hippo pathway outputs, central to understanding core functions.
Key Papers Explained
"Role of YAP/TAZ in mechanotransduction" by Dupont et al. (2011) establishes mechanosensitive regulation of YAP/TAZ, building the framework for growth control. This connects to "Epithelial–mesenchymal transitions in tumour progression" by Thiery (2002), which details EMT processes amplified by YAP/TAZ in cancers. "Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment" by Hanahan and Coussens (2012) extends this to tumor stroma interactions influenced by Hippo dysregulation.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Frontiers center on YAP/TAZ roles in mechanobiology, stem cell regulation, and cancer, based on established works like Dupont et al. (2011). No recent preprints or news in the data indicate ongoing refinements to core mechanisms from top-cited papers.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Epithelial–mesenchymal transitions in tumour progression | 2002 | Nature reviews. Cancer | 6.6K | ✕ |
| 2 | G PROTEINS: TRANSDUCERS OF RECEPTOR-GENERATED SIGNALS | 1987 | Annual Review of Bioch... | 6.4K | ✕ |
| 3 | Akt Phosphorylation of BAD Couples Survival Signals to the Cel... | 1997 | Cell | 5.7K | ✓ |
| 4 | GLUTATHIONE | 1983 | Annual Review of Bioch... | 5.6K | ✕ |
| 5 | Role of YAP/TAZ in mechanotransduction | 2011 | Nature | 5.5K | ✓ |
| 6 | Inhibition of glycogen synthase kinase-3 by insulin mediated b... | 1995 | Nature | 5.2K | ✕ |
| 7 | ASSEMBLY OF ASPARAGINE-LINKED OLIGOSACCHARIDES | 1985 | Annual Review of Bioch... | 4.9K | ✕ |
| 8 | Organization and Expression of Eucaryotic Split Genes Coding f... | 1981 | Annual Review of Bioch... | 4.6K | ✕ |
| 9 | THE HEAT-SHOCK RESPONSE | 1986 | Annual Review of Bioch... | 4.6K | ✕ |
| 10 | Accessories to the Crime: Functions of Cells Recruited to the ... | 2012 | Cancer Cell | 4.6K | ✓ |
Frequently Asked Questions
What is the Hippo pathway?
The Hippo pathway is an evolutionarily conserved signaling cascade initially discovered in Drosophila melanogaster. It regulates tissue growth, organ size control, cell proliferation, and fate decisions. YAP and TAZ act as key downstream effectors that promote transcription of growth-related genes when the pathway is inactive.
What is the role of YAP/TAZ in the Hippo pathway?
YAP and TAZ are transcriptional co-activators inhibited by the Hippo pathway under high cell density or specific signals. When dephosphorylated, they translocate to the nucleus to drive expression of genes involved in proliferation and survival. "Role of YAP/TAZ in mechanotransduction" by Dupont et al. (2011) showed their activation by mechanical stimuli.
How does Hippo pathway signaling control organ size?
Hippo signaling restricts organ size by suppressing YAP/TAZ-mediated proliferation and anti-apoptotic gene expression. Inactivation leads to excessive tissue growth, as observed in Drosophila mutants. The pathway integrates inputs from cell density and mechanical cues to balance growth.
What are the implications of Hippo pathway dysregulation in cancer?
Dysregulated YAP/TAZ activity promotes tumorigenesis by enhancing cell proliferation and epithelial-mesenchymal transition. It connects to tumor microenvironments, as in "Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment" by Hanahan and Coussens (2012). Elevated YAP/TAZ correlates with poor prognosis in various cancers.
How does YAP/TAZ respond to mechanotransduction?
YAP/TAZ sense mechanical signals through cytoskeletal tension and focal adhesions. Stiff matrices or low cell density inactivate Hippo kinases, allowing nuclear YAP/TAZ accumulation. "Role of YAP/TAZ in mechanotransduction" by Dupont et al. (2011) with 5544 citations detailed this mechanism.
What is the current state of research on Hippo pathway and YAP/TAZ?
Research encompasses 27,835 works focused on cell biology applications. Key studies link it to cancer and stem cells, with "Role of YAP/TAZ in mechanotransduction" (2011) as a top-cited paper at 5544 citations. No recent preprints or news coverage were available in the provided data.
Open Research Questions
- ? How do mechanical inputs precisely modulate Hippo kinase activity to control YAP/TAZ localization?
- ? What are the specific YAP/TAZ target genes that drive organ size control across species?
- ? How does Hippo-YAP/TAZ crosstalk with other pathways like Wnt or EMT in tumor progression?
- ? What mechanisms allow YAP/TAZ to integrate cell density and nutrient signals for proliferation?
- ? How can Hippo pathway components be targeted therapeutically in YAP/TAZ-driven cancers?
Recent Trends
The field maintains 27,835 works with no specified 5-year growth rate in the data.
High citation persistence is evident in "Role of YAP/TAZ in mechanotransduction" by Dupont et al. at 5544 citations and earlier works like Thiery (2002) at 6630 citations.
2011No recent preprints or news coverage were provided.
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