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Mechanisms of cancer metastasis
Research Guide
What is Mechanisms of cancer metastasis?
Mechanisms of cancer metastasis are the molecular processes, including signal transduction, gene expression regulation, epithelial-mesenchymal transition, hypoxia response, cell proliferation, and apoptosis, governed by metastasis suppressor genes such as the NDRG family and NM23 that control tumor cell dissemination from primary sites to distant organs.
Research on mechanisms of cancer metastasis encompasses 14,085 works focused on metastasis suppressor genes like NM23 and their roles in regulating low tumor metastatic potential. These studies examine signal transduction, epithelial-mesenchymal transition, and apoptosis in cancer cells. The field highlights genes associated with reduced metastasis in experimental models such as murine K-1735 melanoma cell lines.
Topic Hierarchy
Research Sub-Topics
NDRG Family in Metastasis Suppression
This sub-topic investigates the role of NDRG1, NDRG2, NDRG3, and NDRG4 genes in inhibiting cancer cell migration and invasion. Researchers study their expression regulation under hypoxia and impacts on tumor progression.
Epithelial-Mesenchymal Transition in Metastasis
Research examines EMT mechanisms where epithelial cancer cells acquire mesenchymal traits for enhanced motility and metastasis. Studies focus on transcription factors, signaling pathways, and therapeutic reversal strategies.
Hypoxia Response in Tumor Metastasis
This area explores how low-oxygen microenvironments activate HIF pathways to promote metastatic gene expression and cell survival. Researchers analyze hypoxia-inducible factors and their links to distant tumor seeding.
Signal Transduction in Metastatic Progression
Studies dissect kinase cascades like ERK/MAPK and TGF-β pathways in coordinating metastatic signal relays. Focus includes scaffold proteins and inhibitors modulating cell proliferation and motility.
Apoptosis Regulation in Metastatic Cells
This sub-topic covers evasion of programmed cell death in disseminating cancer cells via suppressor genes and anti-apoptotic proteins. Research evaluates apoptosis induction as a metastasis blockade strategy.
Why It Matters
Understanding mechanisms of cancer metastasis enables identification of suppressor genes that limit tumor spread, with NM23 RNA levels highest in cells and tumors of low metastatic potential in murine K-1735 melanoma and N-nitroso-N-methylurea models, as shown by Steeg et al. (1988) in "Evidence for a Novel Gene Associated With Low Tumor Metastatic Potential". This informs therapies targeting epithelial-mesenchymal transition, a process linking embryonic development and cancer invasiveness detailed by Nieto (2013) in "Epithelial Plasticity: A Common Theme in Embryonic and Cancer Cells". Ror2 signaling's regulation of Golgi structure via IFT20 promotes tumor invasiveness, per Nishita et al. (2017) in "Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness", offering targets for inhibiting metastasis in clinical settings. PTEN deletion in prostate models leads to metastatic cancer, as in Wang et al. (2003) "Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer", guiding genetic interventions.
Reading Guide
Where to Start
"Evidence for a Novel Gene Associated With Low Tumor Metastatic Potential" by Steeg et al. (1988), as it introduces the foundational NM23 metastasis suppressor gene with direct experimental evidence from melanoma models, providing a clear entry to suppressor mechanisms.
Key Papers Explained
Steeg et al. (1988) in "Evidence for a Novel Gene Associated With Low Tumor Metastatic Potential" first identified NM23's link to low metastasis, which Liotta, Steeg, and Stetler-Stevenson (1991) in "Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation" expanded into regulatory balances including NM23. Lambert, Pattabiraman, and Weinberg (2017) in "Emerging Biological Principles of Metastasis" synthesize these into broader principles, while Nishita et al. (2017) in "Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness" details a pro-invasive pathway contrasting suppressors. Wang et al. (2003) in "Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer" builds on this by showing PTEN loss driving metastasis.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Current frontiers emphasize NDRG family suppressors' roles in signal transduction and hypoxia, as per the field's 14,085 papers on metastasis suppressors, though no recent preprints are available. Investigations into epithelial-mesenchymal transition via Nieto (2013) and Ror2 pathways from Nishita et al. (2017) point to Golgi transport and plasticity as active areas.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Ror2 signaling regulates Golgi structure and transport through... | 2017 | Scientific Reports | 15.8K | ✓ |
| 2 | Emerging Biological Principles of Metastasis | 2017 | Cell | 3.0K | ✓ |
| 3 | Cancer metastasis and angiogenesis: An imbalance of positive a... | 1991 | Cell | 2.8K | ✕ |
| 4 | Evidence for a Novel Gene Associated With Low Tumor Metastatic... | 1988 | JNCI Journal of the Na... | 1.3K | ✕ |
| 5 | Prostate-specific deletion of the murine Pten tumor suppressor... | 2003 | Cancer Cell | 1.1K | ✓ |
| 6 | Evaluation of comparative protein modeling by M<scp>ODELLER</scp> | 1995 | Proteins Structure Fun... | 1.1K | ✕ |
| 7 | Coordinating ERK/MAPK signalling through scaffolds and inhibitors | 2005 | Nature Reviews Molecul... | 1.1K | ✕ |
| 8 | Involvement of the TIP60 Histone Acetylase Complex in DNA Repa... | 2000 | Cell | 1.0K | ✓ |
| 9 | TGF-β stimulation and inhibition of cell proliferation: New me... | 1990 | Cell | 970 | ✕ |
| 10 | Epithelial Plasticity: A Common Theme in Embryonic and Cancer ... | 2013 | Science | 965 | ✓ |
Frequently Asked Questions
What role does the NM23 gene play in cancer metastasis?
NM23 is a gene associated with low tumor metastatic potential, with highest RNA levels in cells and tumors from murine K-1735 melanoma cell lines and N-nitroso-N-methylurea models. Steeg et al. (1988) identified it in "Evidence for a Novel Gene Associated With Low Tumor Metastatic Potential". This suppression links to reduced metastatic capacity in experimental systems.
How does Ror2 signaling contribute to tumor invasiveness?
Ror2 signaling regulates Golgi structure and transport through IFT20 to promote tumor invasiveness. Nishita et al. (2017) demonstrated this in "Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness". The pathway affects cellular transport essential for metastatic behavior.
What is the connection between epithelial plasticity and cancer metastasis?
Epithelial plasticity involves epithelial-to-mesenchymal transition (EMT) regulated by transcription factors, epigenetics, and microRNAs, common to embryonic cells and cancer metastasis. Nieto (2013) outlined this in "Epithelial Plasticity: A Common Theme in Embryonic and Cancer Cells". EMT enables cancer cells to migrate and invade distant sites.
How does PTEN loss lead to metastatic prostate cancer?
Prostate-specific deletion of the murine Pten tumor suppressor gene results in metastatic prostate cancer. Wang et al. (2003) showed this in "Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer". PTEN loss disrupts tumor suppression, promoting dissemination.
What are emerging principles of metastasis?
Emerging biological principles of metastasis involve coordinated molecular events beyond initial invasion steps. Lambert, Pattabiraman, and Weinberg (2017) detailed these in "Emerging Biological Principles of Metastasis". Principles include plasticity and microenvironment interactions driving spread.
What balances cancer metastasis and angiogenesis?
Cancer metastasis and angiogenesis reflect an imbalance of positive and negative regulation. Liotta, Steeg, and Stetler-Stevenson (1991) described this in "Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation". Suppressors like NM23 counteract pro-metastatic signals.
Open Research Questions
- ? How do NDRG family metastasis suppressors integrate hypoxia response with epithelial-mesenchymal transition to prevent tumor dissemination?
- ? What specific signal transduction pathways downstream of Ror2 and IFT20 enable Golgi-dependent invasiveness in metastatic cancers?
- ? In what ways do NM23 and PTEN suppressor genes coordinately regulate gene expression to suppress low-metastatic potential in vivo?
- ? How does TGF-β mechanistically switch between stimulating and inhibiting cell proliferation during metastatic progression?
- ? What role do ERK/MAPK scaffolds play in balancing pro- and anti-metastatic apoptosis signals?
Recent Trends
The field maintains 14,085 works on mechanisms of cancer metastasis, with a focus on metastasis suppressors like NDRG family and NM23 regulating epithelial-mesenchymal transition and apoptosis, as described in the core cluster.
Highly cited works such as Nishita et al. "Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness" (15815 citations) dominate, indicating sustained interest in invasiveness pathways without specified 5-year growth data.
2017No recent preprints or news coverage alter these trends.
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