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Signaling Pathways in Disease
Research Guide
What is Signaling Pathways in Disease?
Signaling Pathways in Disease refers to the cluster of biochemical processes centered on Calcineurin-NFAT signaling that regulates transcription and contributes to cancer progression, cardiac hypertrophy, and inflammatory responses, modulated by factors such as Prolyl Isomerase Pin1, EMMPRIN/CD147, and immunophilins.
This field encompasses 36,407 works examining Calcineurin-NFAT signaling in transcriptional regulation. Key modulators include Prolyl Isomerase Pin1, EMMPRIN/CD147, and immunophilins, which influence pathway activity in disease contexts. Growth data over the past 5 years is not available.
Topic Hierarchy
Research Sub-Topics
Calcineurin-NFAT Signaling in Cardiac Hypertrophy
This sub-topic investigates CN-NFAT activation by pressure overload, pathological gene reprogramming, and therapeutic inhibition. Researchers study NFAT dephosphorylation and nuclear translocation in cardiomyocytes.
Calcineurin-NFAT in Cancer Progression
This sub-topic explores NFAT-mediated tumor invasion, angiogenesis, and immune evasion in solid malignancies. Researchers examine CN inhibitors like cyclosporine in metastasis models.
Prolyl Isomerase Pin1 in NFAT Regulation
This sub-topic covers Pin1 isomerization of NFAT phospho-serines, enhancing nuclear retention and activity. Researchers dissect Pin1-NFAT interactions in T-cell activation and hypertrophy.
Immunophilins in Calcineurin Inhibition
This sub-topic analyzes cyclophilin-cyclosporin A and FKBP-FK506 complexes blocking CN phosphatase activity. Researchers probe drug binding kinetics and selectivity in immune suppression.
EMMPRIN/CD147 in Inflammatory Signaling
This sub-topic examines CD147 induction of MMPs and cytokines via NFAT pathways in inflammation. Researchers study its role in leukocyte migration and tissue remodeling.
Why It Matters
Calcineurin-NFAT signaling drives cancer progression, as matrix metalloproteinases facilitate tumor invasion and metastasis, with "New functions for the matrix metalloproteinases in cancer progression" by Egeblad and Werb (2002) detailing their role in extracellular matrix remodeling during malignancy. In cardiac contexts, calcium signaling contributes to hypertrophy, evidenced by "Calcium's Role in Mechanotransduction during Muscle Development" by Benavides Damm and Egli (2014), which links calcium to mechanotransductive responses in muscle cells relevant to heart disease. Inflammatory responses are regulated through inositol trisphosphate and calcium signaling, as Berridge (1993) showed in "Inositol trisphosphate and calcium signalling," impacting immune disorders and tissue repair.
Reading Guide
Where to Start
"Calcium's Role in Mechanotransduction during Muscle Development" by Benavides Damm and Egli (2014) provides an accessible entry into calcium signaling fundamentals relevant to disease mechanotransduction.
Key Papers Explained
"Calcium's Role in Mechanotransduction during Muscle Development" by Benavides Damm and Egli (2014) establishes calcium's mechanotransductive role, building to "Inositol trisphosphate and calcium signalling" by Berridge (1993) and "The versatility and universality of calcium signalling" by Berridge et al. (2000), which expand on calcium's signaling mechanisms. "Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes" by Liu et al. (1991) specifies Calcineurin activation, linking to disease modulation. "Integrins" by Hynes (2002) and "Cell Migration: Integrating Signals from Front to Back" by Ridley et al. (2003) connect to cell motility in pathology.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Research centers on Calcineurin-NFAT transcriptional regulation and modulators like Pin1, EMMPRIN/CD147, and immunophilins in cancer, cardiac hypertrophy, and inflammation, per the cluster description. No recent preprints or news from the last 6-12 months available.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Calcium's Role in Mechanotransduction during Muscle Development | 2014 | Cellular Physiology an... | 14.5K | ✓ |
| 2 | Integrins | 2002 | Cell | 8.4K | ✓ |
| 3 | Inositol trisphosphate and calcium signalling | 1993 | Nature | 6.6K | ✕ |
| 4 | Akt Promotes Cell Survival by Phosphorylating and Inhibiting a... | 1999 | Cell | 6.5K | ✓ |
| 5 | New functions for the matrix metalloproteinases in cancer prog... | 2002 | Nature reviews. Cancer | 6.0K | ✕ |
| 6 | The versatility and universality of calcium signalling | 2000 | Nature Reviews Molecul... | 5.6K | ✕ |
| 7 | Cell Migration: Integrating Signals from Front to Back | 2003 | Science | 4.9K | ✓ |
| 8 | The BCL-2 protein family: opposing activities that mediate cel... | 2007 | Nature Reviews Molecul... | 4.6K | ✕ |
| 9 | Matrix Metalloproteinases and Tissue Inhibitors of Metalloprot... | 2003 | Circulation Research | 4.5K | ✓ |
| 10 | Calcineurin is a common target of cyclophilin-cyclosporin A an... | 1991 | Cell | 4.1K | ✕ |
Frequently Asked Questions
What is the role of Calcineurin in signaling pathways?
Calcineurin serves as a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes, as demonstrated in "Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes" by Liu et al. (1991). This phosphatase activates NFAT transcription factors upon calcium signaling. Its inhibition underlies immunosuppressive therapies in disease.
How does calcium signaling contribute to disease?
Calcium signaling translates mechanical forces into biochemical responses in muscle development and related pathologies like cardiac hypertrophy, per "Calcium's Role in Mechanotransduction during Muscle Development" by Benavides Damm and Egli (2014). It also supports versatility in cellular processes, as outlined in "The versatility and universality of calcium signalling" by Berridge et al. (2000). Dysregulation links to cancer and inflammation.
What are the applications of NFAT signaling research?
NFAT signaling, activated via Calcineurin, regulates transcription in cancer progression and inflammatory responses within this cluster. Modulators like Pin1 and immunophilins alter pathway outcomes in disease models. Findings inform therapies targeting cardiac hypertrophy.
How do integrins participate in signaling pathways in disease?
Integrins mediate cell adhesion and signaling, integrating with pathways like those in cell migration during cancer and atherosclerosis, as reviewed in "Integrins" by Hynes (2002). They polarize migrating cells in disease progression. This connects to mechanotransduction via calcium.
What is the current state of research on this topic?
The field includes 36,407 papers focused on Calcineurin-NFAT signaling and modulators in cancer, cardiac hypertrophy, and inflammation. Top-cited works emphasize calcium's broad roles and targets like Calcineurin. No recent preprints or news coverage from the last 12 months is available.
Open Research Questions
- ? How do Prolyl Isomerase Pin1 and immunophilins specifically interact with Calcineurin-NFAT to alter transcriptional outcomes in cancer?
- ? What mechanisms link EMMPRIN/CD147 modulation to inflammatory responses via this pathway?
- ? How does dysregulation of calcium-Calcineurin signaling contribute to cardiac hypertrophy progression?
- ? Which downstream transcriptional targets of NFAT drive metastasis in cancer models?
Recent Trends
The field maintains 36,407 works with no specified 5-year growth rate.
Focus persists on Calcineurin-NFAT signaling, Pin1, EMMPRIN/CD147, and immunophilins in disease, as no recent preprints or news coverage reported in the last 12 months.
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