Targeting Cell Division Cycle 7 Kinase: A New Approach for Cancer Therapy

Montagnoli, Alessia; Moll, Jürgen; Colotta, Francesco

doi:10.1158/1078-0432.ccr-10-0185

Cited by 104 publications

(108 citation statements)

References 51 publications

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“…5 or 10 M of PHA767491 completely blocked the cell growth (Fig. 2E), consistent with its function in the initiation of DNA replication (25)(26)(27)32). These data suggest that Cdc7 mediates both the cell proliferation and SMC differentiation induced by TGF-␤.…”

Section: Cdc7 Expression Is Increased In Tgf-␤-induced Proliferationsupporting

confidence: 74%

Cell Division Cycle 7 Is a Novel Regulator of Transforming Growth Factor-β-induced Smooth Muscle Cell Differentiation

Shi

Xie

Chen

2012

Journal of Biological Chemistry

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Background: Cell differentiation and proliferation are regulated simultaneously during early development, but the underlying mechanisms remain largely unknown. Results: Cell division cycle 7 (Cdc7) regulates TGF-␤-induced smooth muscle cell differentiation. Conclusion: Cdc7 is likely a common factor regulating both cell proliferation and differentiation. Significance: Our data provide a novel mechanism governing the synchronized regulation of cell proliferation and differentiation.

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Section: Cdc7 Expression Is Increased In Tgf-␤-induced Proliferationsupporting

confidence: 74%

Cell Division Cycle 7 Is a Novel Regulator of Transforming Growth Factor-β-induced Smooth Muscle Cell Differentiation

Shi

Xie

Chen

2012

Journal of Biological Chemistry

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“…Several biopharma companies have initiated Cdc7 drug development programmes, some of which have reached early-stage clinical trials [130,131]. First-in-class Cdc7 inhibitors have broad tumour spectrum activity in preclinical models, consistent with loss of the protective checkpoint mechanism in most tumour types.…”

Section: The Dna Replication Initiation Machinery-a Promising Anti-camentioning

confidence: 99%

The cell cycle and cancer

Williams

Stoeber

2011

The Journal of Pathology

534

385

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Deregulation of the cell cycle underlies the aberrant cell proliferation that characterizes cancer and loss of cell cycle checkpoint control promotes genetic instability. During the past two decades, cancer genetics has shown that hyperactivating mutations in growth signalling networks, coupled to loss of function of tumour suppressor proteins, drives oncogenic proliferation. Gene expression profiling of these complex and redundant mitogenic pathways to identify prognostic and predictive signatures and their therapeutic targeting has, however, proved challenging. The cell cycle machinery, which acts as an integration point for information transduced through upstream signalling networks, represents an alternative target for diagnostic and therapeutic interventions. Analysis of the DNA replication initiation machinery and mitotic engine proteins in human tissues is now leading to the identification of novel biomarkers for cancer detection and prognostication, and is providing target validation for cell cycle-directed therapies.

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“…Inhibition of Cdc7 kinase activity results in a decrease of Mcm2 phosphorylation, restricts DNA replication, and induces apoptotic cell death (60,234). Several Cdc7 inhibtors have been analyzed in preclinical studies, and two of these inhibitors are currently in phase I clinical development (233,318).…”

Section: Inhibiting Celt Cycte Entry or Progressionmentioning

confidence: 99%

Physiological Relevance of Cell Cycle Kinases

Malumbres

2011

Physiological Reviews

176

135

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The basic biology of the cell division cycle and its control by protein kinases was originally studied through genetic and biochemical studies in yeast and other model organisms. The major regulatory mechanisms identified in this pioneer work are conserved in mammals. However, recent studies in different cell types or genetic models are now providing a new perspective on the function of these major cell cycle regulators in different tissues. Here, we review the physiological relevance of mammalian cell cycle kinases such as cyclin-dependent kinases (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1, BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek proteins, or Mastl and their implications in development, tissue homeostasis, and human disease. Among these functions, the control of self-renewal or asymmetric cell division in stem/progenitor cells and the ability to regenerate injured tissues is a central issue in current research. In addition, many of these proteins play previously unexpected roles in metabolism, cardiovascular function, or neuron biology. The modulation of their enzymatic activity may therefore have multiple therapeutic benefits in human disease.

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Targeting Cell Division Cycle 7 Kinase: A New Approach for Cancer Therapy

Cited by 104 publications

References 51 publications

Cell Division Cycle 7 Is a Novel Regulator of Transforming Growth Factor-β-induced Smooth Muscle Cell Differentiation

Cell Division Cycle 7 Is a Novel Regulator of Transforming Growth Factor-β-induced Smooth Muscle Cell Differentiation

The cell cycle and cancer

Physiological Relevance of Cell Cycle Kinases

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