图书馆订阅: Guest
Begell Digital Portal Begell 数字图书馆 电子图书 期刊 参考文献及会议录 研究收集
肿瘤形成评论综述™
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN 打印: 0893-9675
ISSN 在线: 2162-6448

肿瘤形成评论综述™

DOI: 10.1615/CritRevOncog.v7.i3-4.70
pages 261-291

Oncogene-lnitiated Aberrant Signaling Engenders the Metastatic Phenotype: Synergistic Transcription Factor Interactions are Targets for Cancer Therapy

David T. Denhardt
Department of Cell, Developmental and Neurobiology and The Cancer Institute of New Jersey; Nelson Biological Laboratories, Rutgers University

ABSTRACT

Certain p21GTPases (notably Ras) and some of their guanine nucleotide exchange factors (e.g., Ost, Dbl, Tiam) and downstream mediators (e.g., Raf, Мус) have the potential to promote the development of malignancies because they can enhance the transcription of genes that foster the tumorigenic and metastatic phenotype. Among these are genes that stimulate cell proliferation, confer immortality, and facilitate the invasion of normal tissues. Oncogenes upstream of Ras—cell surface receptors such as ErbB2/Neu, Met, or Trk (and their ligands), and nonreceptor cytoplasmic protein tyrosine kinases such as Src and Abl—not only can act through Ras but also contribute additional signals. This review presents a synopsis of our understanding of signaling pathways controlled by the p21GTPases, with a focus on transcription factors regulated by the pathways. Mutations in one or more of the elements in these signaling pathways are invariably found in cancer cells. Crosstalk among the pathways may explain how some forms of stress can contribute to the development of a malignancy. Abnormal signaling leads to modified cytoskeletal structures and permanently altered (i.e., self-sustaining or epigenetic) transcription of target genes. A common theme is that genes whose transcription is elevated to the greatest extent by Ras often have in their promoters juxtaposed binding sites for two different transcription factors (particularly those in the Fos/Jun, CREB/ATF, NFκB, and Ets families) each of which is activated and such that together they synergize to augment transcription substantially. Some of these transcription factors can also act as oncogenes in certain cell types when appropriately modified and expressed. This unifying theme among many different cancers suggests that strategies to restore the balance among the signaling pathways or to suppress synergistic interactions between transcription factors may prove broadly useful in reversing the malignant phenotype.


Articles with similar content:

Cross-Regulation Between WNT and NF-κB Signaling Pathways
Forum on Immunopathological Diseases and Therapeutics, Vol.1, 2010, issue 3
Qiang Du, David Geller
Mechanisms of Integrin-Mediated Virus Attachment and Internalization Process
Critical Reviews™ in Immunology, Vol.21, 2001, issue 4
Kathy Triantafilou, Martha Triantafilou
Histone Acetyltransferases in Cancer: Guardians or Hazards?
Critical Reviews™ in Oncogenesis, Vol.22, 2017, issue 3-4
Antonis Kirmizis, Christina Demetriadou
Epigenetic/Genetic Mismatch: Using Transdifferentiation as a Potential Cancer Therapy to Exploit the Cell Type Specificity of Cancer
Critical Reviews™ in Oncogenesis, Vol.20, 2015, issue 5-6
Devasis Chatterjee, Andrew R. Mendelsohn, Jennifer L. Lei
A Compilation and Classification of DNA Binding Sites for Protein Transcription Factors from Vertebrates
Critical Reviews™ in Eukaryotic Gene Expression, Vol.4, 1994, issue 2-3
Teni Boulikas