CDK4: A Key Player in the Cell Cycle, Development, and Cancer

Baker, Stacey J.; Reddy, E. Premkumar

doi:10.1177/1947601913478972

Cited by 183 publications

(145 citation statements)

References 159 publications

(278 reference statements)

Supporting

Mentioning

139

Contrasting

Unclassified

Order By: Relevance

“…Known as oncogenes involved in cell-cycle regulation and progression, MDM2 and/or CDK4 has been implicated in a wide spectrum of human cancers. [20][21][22][23][24][25] In dedifferentiated liposarcoma, for instance, amplification of MDM2 is nearly always accompanied by CPM, HMGA2, and YEATS4 in the same amplicon, while CDK4 can sometimes have GLI1 and DDIT3 as the amplification partners. 26,27 These findings are similar to what has been observed in our adenosarcoma cases.…”

Section: Discussionmentioning

confidence: 99%

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

Lee

Changou

et al. 2016

Modern Pathology

View full text Add to dashboard Cite

Müllerian adenosarcomas are malignant gynecologic neoplasms. Advanced staging and sarcomatous overgrowth predict poor prognosis. Because the genomic landscape remains poorly understood, we conducted this study to characterize the genomewide copy number variations in adenosarcomas. Sixteen tumors, including eight with and eight without sarcomatous overgrowth, were subjected to a molecular inversion probe array analysis. Copy number variations, particularly losses, were significantly higher in cases with sarcomatous overgrowth. Frequent gains of chromosomal 12q were noted, often involving cancer-associated genes CDK4 (six cases), MDM2, CPM, YEATS4, DDIT3, GLI1 (five each), HMGA2 and STAT6 (four), without association with sarcomatous overgrowth status. The most frequent losses involved chromosomes 13q (five cases), 9p, 16q and 17q (four cases each) and were almost limited to cases with sarcomatous overgrowth. MDM2 and CDK4 amplification, as well as losses of RB1 (observed in two cases) and CDKN2A/B (one case), was verified by FISH. By immunohistochemistry, all MDM2/CDK4-coamplified cases were confirmed to overexpress both encoded proteins, whereas all four cases with (plus an additional four without) gain of HMGA2 overexpressed the HMGA2 protein. Both cases with RB1 loss were negative for the immunostaining of the encoded protein. Chromothripsis-like copy number profiles involving chromosome 12 or 14 were observed in three fatal cases, all of which harbored sarcomatous overgrowth. With whole chromosome painting and deconvolution fluorescent microscopy, dividing tumor cells in all three cases were shown to have scattered extrachromosomal materials derived from chromosomes involved by chromothripsis, suggesting that this phenomenon may serve as visual evidence for chromothripsis in paraffin

show abstract

Section: Discussionmentioning

confidence: 99%

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

Lee

Changou

et al. 2016

Modern Pathology

View full text Add to dashboard Cite

show abstract

“…A fundamental aspect of cancer is the dysregulation of cell cycle control. Alterations in the machinery that controls G 1 /S transition are frequently observed in many types of human cancers [43][44][45]. For instance, amplification of CCND1 gene or overexpression of Cyclin D1 protein has been found in a wide spectrum of human cancers [46,47].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-188 suppresses G 1 /S transition by targeting multiple cyclin/CDK complexes

et al. 2014

Cell Communication and Signaling

View full text Add to dashboard Cite

Background: Accelerated cell cycle progression is the common feature of most cancers. MiRNAs can act as oncogenes or tumor suppressors by directly modulating cell cycle machinery. It has been shown that miR-188 is upregulated in UVB-irradiated mouse skin and human nasopharyngeal carcinoma CNE cells under hypoxic stress. However, little is known about the function of miR-188 in cell proliferation and growth control. Results: Overexpression of miR-188 inhibits cell proliferation, tumor colony formation and G 1 /S cell cycle transition in human nasopharyngeal carcinoma CNE cells. Using bioinformatics approach, we identify a series of genes regulating G 1 /S transition as putative miR-188 targets. MiR-188 inhibits both mRNA and protein expression of CCND1, CCND3, CCNE1, CCNA2, CDK4 and CDK2, suppresses Rb phosphorylation and downregulates E2F transcriptional activity. The expression level of miR-188 also inversely correlates with the expression of miR-188 targets in human nasopharyngeal carcinoma (NPC) tissues. Moreover, studies in xenograft mouse model reveal that miR-188 is capable of inhibiting tumor initiation and progression by suppressing target genes expression and Rb phosphorylation.

show abstract

“…This is seen with highest prevalence in well-differentiated and dedifferentiated liposarcoma, a disease in which CDK4 amplification is nearly universal (5,6). CDK4 amplification has also been observed at lower frequency in other solid tumors and hematologic malignancies (4). (iii) Activating mutation of CDK4.…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways: CDK4 Inhibitors for Cancer Therapy

Dickson

2014

Clinical Cancer Research

217

179

View full text Add to dashboard Cite

Unrestrained growth is the hallmark of cancer, and disrupted cell-cycle regulation is, therefore, common. CDK4 is the key regulator of the G 1 -S transition. In complex with cyclin D, CDK4 phosphorylates retinoblastoma protein (Rb) and drives cell-cycle progression, a process inhibited by p16. The p16-CDK4-cyclin D-Rb is aberrant in the majority of cancers and is, thus, a logical target for anticancer therapy. Previous attempts to block CDK4 with nonselective cyclin-dependent kinase (CDK) inhibitors led to toxicity and little efficacy. However, the recent development of selective CDK4 inhibitors launched the first successful efforts to target the pathway for cancer therapy. Three oral selective CDK4 inhibitors have entered clinical trials: palbociclib (PD0332991), LEE011, and LY2835219. CDK4 inhibitors have in vitro activity against a broad range of cancers and in patients have shown antitumor activity in breast cancer, lymphoma, sarcoma, and other tumors. Major efforts are under way to develop biomarkers of response, understand potential mechanisms of resistance, and develop rational combinations of CDK4 inhibitors with chemotherapy and other targeted drugs. Clin Cancer Res; 20(13); 3379-83. Ó2014 AACR.

show abstract

CDK4: A Key Player in the Cell Cycle, Development, and Cancer

Cited by 183 publications

References 159 publications

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

MicroRNA-188 suppresses G 1 /S transition by targeting multiple cyclin/CDK complexes

Molecular Pathways: CDK4 Inhibitors for Cancer Therapy

Contact Info

Product

Resources

About