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Currently, intensive effort is being directed toward the identification of molecular targets that can provide approaches to the development of novel therapeutic strategies in cancer management. This book focuses on metastasis-associated genes, metastasis promoter and suppressor genes, which relate specifically to behavioral alterations of cancer cells in epithelial mesenchymal transition, cancer stem cell maintenance and propagation, and to the acquisition of invasive and metastasis faculty. The function of these genes has implications for cell cycle regulation and cell proliferation and so constitute an essential element in cancer growth and dissemination. The emphasis in this book is on how appropriate these genes are as molecular targets and how practicable are the constituents of their signal transduction systems as potential candidates and how accessible they are to targeted therapy. Written in a straightforward and clear style with background information supporting the new research, this book will be useful for students and researchers in cancer therapies.
- Identifies molecular targets and their accessibility for therapeutic intervention
- Provides information on biological features of tumor development and dissemination
- Background information provided for each topic
Developmental biologists, cell biologists and cancer researchers
Part 1: RNA Interference in Genetic Regulation
1. The Biogenesis and Functions of MicroRNAs
2. Association of miRNAs with Pathogenesis
The Genesis of DiGeorge Syndrome
Association of the Glyoxalase Pathway with miRNA Function
3. Are miRNAs Suitable Targets for Cancer Therapy?
A Resumé of mTOR Signalling
miRNAs, Cell Proliferation and Apoptosis
miRNAs in EMT, and Cell Motility and Invasion
miRNAs and Tumour Angiogenesis
miRNAs, Tumour Growth, Invasion and Metastasis
miRNAs and Chemo/Radiosensitivity of Tumours
The Therapeutic Potential of miRNAs
Part 2: EMT Associated Gene Targeting
4. Hedgehog Signalling in EMT
5. Targeted Inhibition of Hh, Wnt, TGF-β Signalling Complex
SMO Is a GPCR Component of Hh Signalling
Small Molecule Inhibitors of SMO
HDAC Inhibitors Combination with Hh Inhibition
Targeting Gli1 in Deregulated Hh Signalling
6. Encountering Aberrant Wnt Signalling
The Canonical and Non-canonical Wnt Routes of Signalling
Fzd and LRP Inhibition, Dkk and SFRPs
Fzd and DVL Interaction
7. Therapeutic Targeting of TGF-β Signalling
Antisense Oligonucleotide Trabedersen (AP 12009)
Anti-TGF-β Monoclonal Antibodies
Small Molecule Inhibitors of the TGF-β Receptor Family
Inhibition of Type RIII Function
8. EGFR Signalling in EMT
E-cadherin in EGFR Signalling
EGFR Signalling Path to EMT
ECM and Cell Membrane Components in EGFR Signalling
EGFR and TGF-β Signalling Pathways Interact in EMT
Part 3: Therapeutic Deployment of Metastasis-Associated Gene Function
9. S100A4 as a Potential Target
The Spectrum of Biological Function of S100A4
Influence of Wnt Signalling on S100A4 Expression
Osteopontin an Intermediary Target of S100A4
RAGE/NF-κB Signalling in S100A4 Function
S100A4 Downregulates PRDM1 and VASH1 Suppressor Genes
S100A2 Suppressor Gene and S100A4 Function
10. MTAs in Cancer Invasion and Metastasis
The Biology of Metastasis Promotion by MTAs
Modulation/Inhibition of MTA Expression
MTA Signalling Intercalates with Wnt/Notch/Hh Signalling
Part 4: Genetic Determinants of Tumour and Metastasis Suppression
11. Metastasis Suppressor nm23 and Manipulation of its Expression
Manipulation of nm23 Expression as a Therapeutic Approach
Upregulation of nm23 by Medroxyprogesterone Acetate
Targeting S100A4 to Restore nm23 Function
Is Tumor Suppressor p53 a Route to nm23 Manipulation?
12. The Metastasis Suppressor KiSS-1 Gene
The Tumor Suppressor Function of Kisseptin
Kisseptin in Clinical Medicine
13. KAI1 (CD82) Suppresses Metastasis, Cell Proliferation and Invasion
Reactivation of KAI1
14. 14-3-3 Proteins in Normal and Tumour Cell Biology
Expression of 14-3-3σ in Tumour Progression
How Do Other 14-3-3 Isoforms Perform in the Clinical Settting?
14-3-3 Proteins in Regulation of Cell Proliferation
P53 in 14-3-3 Function
The Function of 14-3-3 via PI3K/Akt Survival Pathway
Growth Factors and Their Receptors in 14-3-3 Function
Regulation of Cell Cycle Checkpoints by 14-3-3 Proteins
Do 14-3-3 Proteins Participate in DNA Repair?
14-3-3σ and NF-κB Survival Pathway
Does 14-3-3σ Influence Wnt Signalling?
14-3-3 and Hh Signalling
14-3-3 Proteins Interact with RASSF Signalling
Do 14-3-3 Proteins Employ mTOR Signalling?
Effects of 14-3-3 Proteins on Cell Motility and Invasion
Therapeutic Approach with 14-3-3
15. Suppressor Function of NDRG1
NDRG1 Suppresses MMP Activity and Invasion
Upregulation of NDRG1 Suppresses Cell Migration and Proliferation
Regulation of Cell Proliferation by NDRG1 Mediated by p53
Oestradiol and NDRG1 Expression
Metastasis Suppression by NDRG1
16. The ING (Inhibitor of Growth) Suppressor Gene
17. The BRCA1 and BRCA2 Suppressor Genes
18. BRMS1 (Breast Cancer Metastasis Suppressor 1) Gene
19. Maspin (SerpinB5): A Postulated Tumour Suppressor
20. EPB41L3 and CADM1 Tumour Suppressor Function
Part 5: Signalling and Transcription Regulators as Prospective Candidates in Cancer Therapy
Part 5. Signalling and Transcription Regulators as Prospective Candidates in Cancer Therapy
21. Is MKK a Metastasis Suppressor?
The MAPK Signalling Pathway
MKK in Tumour Biology
The Inhibitory Effects of Anthrax Lethal Toxin on MKKs
LeTx and Cell Invasion/Motility
LeTx Inhibits Angiogenesis
22. RKIP Suppresses Invasion and Metastasis
RKIP Downregulation Creates Chromosomal Instability and Abnormalities
RKIP Inhibits Invasion and Growth of Cancer
RKIP Downregulation is a Frequent Event in Cancer
Pathways of RKIP Signalling
Effects of Re-expression of RKIP on Metastatic Spread
23. CRSP3 Metastasis Suppressor
24. The Suppressor Function of TXNIP
TXNIP in Cell Proliferation and Apoptosis
TXNIP and Angiogenesis
miRNAs in TXNIP Function
25. The Essence of the Hippo Signalling System
Lats (Large Tumour Suppressor) Gene Signals via Hippo
Hippo in Cross Talk with Growth Factor Signalling
Upstream Regulators of Hippo Are Tumour Suppressors
RASSF Genes Are Silenced in Tumours
RASSFs Regulate Cell Proliferation and Apoptosis
The N-terminal RASSFs May Be Tumour Promoters
26. HIC1 Suppressor Gene
Silencing of HIC1 in Tumours
A Resumé of Apoptosis Pathways
The Alternative Reading Frame Tumour Suppressor Genes
ARFs and Bmi-1 Function
ARF Function and p53 Activity
ARF Interactions with CtBP
Do ARFs Function in Conjunction with 14-3-3σ?
The PARP Pathway
HIC1 is a Downstream Target of p53
HIC1 Can Function Independently of p53
27. The DLC Suppressor Genes
Effects of Re-expression of DLC1
DLC Expression in Metastatic Spread
28. The LKB1 (STK11) Suppressor Gene
Expression of LKB1 and Tumorigenesis
LKB1 Suppresses Invasion and Metastasis
Signalling Systems in Cross Talk with LKB1
LKB1 in Cross Talk with Oestrogens and ER/HER2
LKB1 Suppresses EMT
LKB1 and Stem Cell Survival and Pluripotency
LKB1, Cytoskeletal Dynamics and Cell Motility and Invasion
Therapeutic Assessment of LKB1
AMPK as a Therapeutic Target
AICAR (5-aminoimidazole-4-carboxamide 1-D-ribonucleoside)
Metformin Activates AMPK
Does Metformin Selectively Destroy CSCs?
Application of Metformin in Cancer Management
29. PLCD1 Suppresses Tumorigenesis
Loss of PLCD1 Expression in Tumours and its Biological Outcome
30. Inhibitor of DNA Binding Proteins in Tumours
Is ID4 a Tumour Suppressor?
ID1, ID2 and ID3 Expression in Tumours
IDs and Tumour Angiogenesis
IDs in Cancer Stem Cell Propagation and Maintenance
Do ID Proteins Activate Other Signalling Systems and Promote Cell Proliferation?
Are IDs Suitable Therapeutic Targets?
31. PDCD4 (Programmed Cell Death 4)
Can PDCD4 Be Manipulated for Therapy?
- No. of pages:
- © Elsevier 2013
- 31st July 2013
- Hardcover ISBN:
- eBook ISBN:
Dr. Gajanan V. Sherbet is Doctor of Science of London University and Fellow of the Royal College of Pathologists and the Royal Society of Chemistry. He is member of the editorial boards of many scientific and medical journals, and formerly editor of Experimental Cell Biology and Pathobiology. Dr. Sherbet’s major scientific interest is in cancer metastasis. He has focused on the role of growth factors and their signaling, and the calcium binding protein S100A4 in cell proliferation, cancer invasion and metastasis; also he is currently studying the potential of artificial neural networks for predicting breast cancer progression and prognosis. Dr. Sherbet has numerous scientific papers in international journals and has written and edited several books on cancer, such as Growth Factors and Their Receptors in Cell Differentiation, Cancer and Cancer Therapy (2011) and Therapeutic Strategies in Cancer Biology and Pathology (2013), and e-books on the role of growth factors and their receptors in cancer therapy and therapeutic strategies in cancer biology and molecular pathology.
Professor, Institute for Molecular Medicine, Huntington Beach CA, USA and Professor (visiting), School of Electrical and Electronic Engineering, University of Newcastle upon Tyne, UK
"The major motivation for this volume on cancer therapeutic strategies is to identify items of therapeutic interest in the biological functioning of high-profile metastasis suppressor and promoter genes and uncover links and nodes of their signaling pathways in order to directly or indirectly countermand the biological effects of these genes."--Reference & Research Book News, December 2013
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