Clinical Aggressiveness of Myxofibrosarcomas Associates with Down-Regulation of p12CDK2AP1: Prognostic Implication of a Putative Tumor Suppressor that Induces Cell Cycle Arrest and Apoptosis Via Mitochondrial Pathway

Li, Chien‐Feng; Huang, Hsuan-Ying; Wu, Wen‐Ren; Liang, Shih‐Shin; Chen, Lih-Ren; Peng, Yung-Hsing; Lee, Hui-Chieh; Shiue, Yow‐Ling

doi:10.1245/s10434-014-3825-0

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…Furthermore, downregulation of CDK2 induces high tumor suppressor p12 levels, thereby, inducing MFS cell cycle arrest and apoptosis. Vice versa, a low p12 level is a poor prognostic factor in patients with MFSs [ 123 ]. So far, unfortunately, the aforementioned findings and knowledge about potential targets such as CDK6 or CDK2 have not resulted in a clinical trial in MFSs.…”

Section: Cdk Pathway Dysregulation In Prevalent Stssmentioning

confidence: 99%

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

Thiel

Daigeler

Kolbenschlag

et al. 2022

Cancers

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Soft tissue sarcomas (STSs) are tumors that are challenging to treat due to their pathologic and molecular heterogeneity and their tumor biology that is not yet fully understood. Recent research indicates that dysregulation of cyclin-dependent kinase (CDK) signaling pathways can be a strong driver of sarcogenesis. CDKs are enzyme forms that play a crucial role in cell-cycle control and transcription. They belong to the protein kinases group and to the serine/threonine kinases subgroup. Recently identified CDK/cyclin complexes and established CDK/cyclin complexes that regulate the cell cycle are involved in the regulation of gene expression through phosphorylation of critical components of transcription and pre-mRNA processing mechanisms. The current and continually growing body of data shows that CDKs play a decisive role in tumor development and are involved in the proliferation and growth of sarcoma cells. Since the abnormal expression or activation of large numbers of CDKs is considered to be characteristic of cancer development and progression, dysregulation of the CDK signaling pathways occurs in many subtypes of STSs. This review discusses how reversal and regulation can be achieved with new therapeutics and summarizes the current evidence from studies regarding CDK modulation for STS treatment.

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Section: Cdk Pathway Dysregulation In Prevalent Stssmentioning

confidence: 99%

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

Thiel

Daigeler

Kolbenschlag

et al. 2022

Cancers

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Cell cycle and apoptosis regulatory proteins, proliferative markers, cell signaling molecules, CD209, and decorin immunoreactivity in low-grade myxofibrosarcoma and myxoma

2015

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The histologic differential diagnosis between intramuscular myxoma and low-grade myxofibrosarcoma can be quite difficult in some cases. To identify a diagnostic immunohistochemical marker, we compared the staining profiles of 19 different antigens, including cell cycle proteins, apoptosis proteins, and proliferative markers, and selected other signaling and structural proteins in these two tumors. Ten cases each of intramuscular myxoma and low-grade myxofibrosarcoma were stained with antibodies directed against apoptosis regulatory proteins (Bcl2, activated caspase-3, phospho-H2A.X, and cleaved PARP), cell cycle regulatory proteins (Rb1, Cyclin-A, CDKN1B, and Cdt1), proliferative markers (KI67, MCM2, phospho-histone H3, and geminin), cell signalling molecules (c-Myc, EGF, EGFR, PLA2G4A, and HSP90), a dendritic cell marker (CD209), and the extracellular matrix proteoglycan decorin. Staining patterns of myxoma and myxofibrosarcoma were compared using Fisher's exact test and the Mann-Whitney test. For each potential diagnostic marker studied, the proportions of cases scored as positive on both dichotomous or ordinal scales were not significantly different between myxoma and myxofibrosarcoma. Myxoma and myxofibrosarcoma share a common immunophenotype for each of the markers studied. Distinction between these tumors is still predominantly based on morphologic criteria.

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Clinical Aggressiveness of Myxofibrosarcomas Associates with Down-Regulation of p12CDK2AP1: Prognostic Implication of a Putative Tumor Suppressor that Induces Cell Cycle Arrest and Apoptosis Via Mitochondrial Pathway

Abstract: Through down-regulation of CDK2, high p12(CDK2AP1) level induced cell cycle arrest and the mitochondrial-dependent apoptotic pathway. Low p12(CDK2AP1) level represents a poor prognostic factor in patients with myxofibrosarcoma.

Cited by 2 publications

References 35 publications

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

Cell cycle and apoptosis regulatory proteins, proliferative markers, cell signaling molecules, CD209, and decorin immunoreactivity in low-grade myxofibrosarcoma and myxoma

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