Cell cycle regulating proteins p21 and p27 in prognosis of oral squamous cell carcinomas

Fillies, Thomas; Woltering, Mike; Brandt, Burkhard; Diest, Jean Paul Van; Werkmeister, R.; Joos, Ulrich; Buerger, Horst

doi:10.3892/or.17.2.355

Cited by 45 publications

(66 citation statements)

References 18 publications

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“…17 In the current study, we found PKM2 could interact with p27, and decreased level of p27 in PKM2 specific siRNA-transfected astrocyte cells. Thus, PKM2 also might negasitive regulate p27 following SCI and the repair process, and further influence the cyclin E/ CDK2 in cell cycle progression.…”

Section: Discussionsupporting

confidence: 51%

“…p27 Kip1 (p27) is a key cell-cycle regulator, which negatively regulates cell cycle progression via inhibiting the cyclinE/CDK2 complexes directly. 17,18 The activity of p27 is controlled by its concentration, distribution among different cellular complexes, and its cellular location. 19,20 The final step in glycolysis is catalyzed by Pyruvate kinase (PK) via transferring the phosphate from phosphoenolpyruvate (PEP) to ADP, thereby generating pyruvate and ATP.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

et al. 2015

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Department of Stomatology; Affiliated Hospital of Nantong University, Nantong; Nantong University; 226001, Nantong, Jiangsu, PR China y These authors equally contributed to this work, and should be considered as joint first authors.Keywords: astrocyte proliferation, b-catenin, p27, PKM2, spinal cord injuryAbbreviations: CNS, Central nervous system; CDKs, cyclin-dependent kinases; CAK, CDK activating kinase; E2F, E2 promoter-binding protein dimerization partners; GFAP, Glial fibrillary acidic protein; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; NeuN, Neuronal nuclei; PCNA, Proliferating cell nuclear antigen; PEP, phosphoenolpyruvate; PK, Pyruvate kinase; PKM2, pyruvate kinase M2; pRb, protein retinoblastoma; SCI, Spinal cord injury; EGFR, Epidermal growth factor receptor.Aberrant functionality of the cell cycle has been implicated in the pathology of traumatic SCI. Although it has been reported that the expressions of various cell cycle related proteins were altered significantly following SCI, detailed information on the subject remains largely unclear. The embryonic pyruvate kinase M2 (PKM2) is an important metabolic kinase in aerobic glycolysis or the warburg effect, however, its functions in central nervous system (CNS) injury remains elusive. Here we demonstrate that PKM2 was not only significantly upregulated by western blot and immunohistochemistry but certain traumatic stimuli also induced translocation of PKM2 into the nucleus in astrocytes following spinal cord injury (SCI). Furthermore, the expression levels and localization of p-b-catenin, p27, cyclin D1 and PCNA were correlated with PKM2 after SCI. In vitro, we also found that PKM2 co-immunoprecipitation with p-b-catenin and p27 respectively. Knockdown of PKM2 apparently decreased the level of PCNA, cyclinD1, p27 in primary astrocyte cells. Taken together, our findings indicate that nuclear translocation of PKM2 promotes astrocytes proliferation after SCI through modulating cell cycle signaling. These discoveries firstly uncovered the role of PKM2 in spinal cord injury and provided a potential therapeutic target for CNS injury and repair.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

et al. 2015

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“…The p27 protein is structurally homologous to the p21 protein; p27 expression leads to the arrest of the cell cycle, and is increased by growth inhibition signals, while it is decreased by growth stimulating signals, leading to cell cycle progression (18).…”

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confidence: 99%

The Role of p16, p21, p27, p53 and Ki-67 Expression in the Differential Diagnosis of Cutaneous Squamous Cell Carcinomas and Keratoacanthomas: An Immunohistochemical Study

et al. 2016

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“…Fillies et al 38 reported that increased HIF-1 alpha expression was associated with good prognosis in early stage squamous cell carcinoma of the oral floor, but they speculated that expression of HIF-1 alpha is not hypoxia related but is due to alterations in oncogene or tumor suppressor genes. Therefore, we investigated the prognosis of patients with OSCC in stage I, II and stage III, IV, respectively, to investigate the different behavior of HIF-1 alpha expression between early stage OSCC and advanced stage OSCC in the present study.…”

Section: Pcna Immunohistochemistry and Labeling Indicesmentioning

confidence: 99%

Hypoxia-inducible factor 1 alpha in oral squamous cell carcinoma and its relation to prognosis

et al. 2009

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The aim of this study was to investigate the correlation between the expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and proliferative activity in tumor cells, lymph node metastasis, as well as prognosis in patients with oral squamous cell carcinoma (OSCC). Fifty-seven biopsy specimens of OSCC were investigated for the expression of HIF-1 alpha and proliferating cell nuclear antigen (PCNA) by immunohistochemistry. None of the patients had received any prior treatments. The percentage of HIF-1 alpha immunopositive area (PHIA) was calculated using computer-assisted image analysis for quantitative assessment of HIF-1 alpha expression.The PCNA labeling index (LI) was evaluated as a proliferation maker. We found that the mean PHIA in all stages was 12.1% in the poor prognosis patients, and it was 6.4% in the good prognosis patients. There was a significant difference of PHIA between poor prognosis and good prognosis patients (P=0.0065). Furthermore, the mean PHIA in the patients who had no metastatic lymph nodes was 7.5%, while it was 11.7% in the patients who had metastatic lymph nodes. There was also a significant difference of PHIA between patients who had no metastatic lymph nodes and those who had metastatic lymph nodes (P=0.0487). On the other hand, significant correlation between PHIA and PCNA LI was not observed. These results provide the clinical data 3 indicating that HIF-1 alpha may play an important role in lymph node metastasis and prognosis in patients with OSCC.

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Cell cycle regulating proteins p21 and p27 in prognosis of oral squamous cell carcinomas

Cited by 45 publications

References 18 publications

Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

The Role of p16, p21, p27, p53 and Ki-67 Expression in the Differential Diagnosis of Cutaneous Squamous Cell Carcinomas and Keratoacanthomas: An Immunohistochemical Study

Hypoxia-inducible factor 1 alpha in oral squamous cell carcinoma and its relation to prognosis

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