Activation of ERK1/2 and cyclin D1 expression in oral tongue squamous cell carcinomas: Relationship between clinicopathological appearances and cell proliferation

Wang, Lihong; Liu, Tingjiao; Nishioka, Mai; Aguirre, Rodelio L.; Win, Swe Swe; Okada, Norihiko

doi:10.1016/j.oraloncology.2005.11.002

Cited by 45 publications

(37 citation statements)

References 31 publications

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“…In agreement, Gao et al suggested that activation of the c-Raf-MEK-Erk1/2 pathway leads to subsequent increase in cell cycle proteins (cyclin D1, p27kip1), accompanied by an increased growth rate and transition of cells from G0/G1 into the S phase of the cell cycle in both ovarian and non-small cell lung cancer (47). Similarly, Wang et al indicated that overexpression of activated Erk1/2 and cyclin D1 proteins are involved in oral tongue carcinogenesis (51). Finally, Judd et al (59) reported that MEK1 activation enhances CD44 expression and promotes aggressiveness in HNSCC, while Katada et al (60) and Zuo et al (61) suggested that Erk1/2 activation correlates with increased cell migration and invasion in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

et al. 2014

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Abstract. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway possesses confirmed oncogenic potential in oral squamous cell carcinoma (OSCC). Crosstalk with other molecular pathways contributes to STAT3 regulation in cancer. The effects of mitogen-activated protein kinases (MAPKs) and particularly extracellular signal-regulated kinase 1/2 (Erk1/2) on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examined the effects of Erk1/2 modulation on STAT3 signaling and cell growth in OSCC cells. Constitutive expression levels of phosphorylated (tyrosine and serine) and total STAT3, Erk1/2 and cyclin D1 were assessed in OSCC cell lines. Erk1/2 modulation was achieved by pharmacological agents; siRNA silencing against Erk1/2 was also performed. Cell proliferation and viability were assessed. Erk1/2 inhibition with either U0126 treatment or specific siRNA silencing resulted in decreases in p-ser STAT3 and cyclin D1 levels and increases in p-tyr STAT3 in OSCC cells. Moreover, Erk1/2 inhibition resulted in a dose-dependent reduction in OSCC cell growth and viability. Erk1/2 induction had the opposite effects. Taken together, these results are supportive of an active crosstalk between the oncogenic Erk1/2 and STAT3 pathways in OSCC, the significance of which requires further investigation.

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Section: Discussionmentioning

confidence: 99%

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

et al. 2014

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“…In contrast to OGG1, Maspin and phospho-Src, which were reduced, we found an increase in the levels of the salivary CysD1, Ki67, LDH and MMP-9 in the OSCC patients. CycD1 and Ki67 are cell-cycle regulators, which have been shown to be correlated with cellular proliferation and tumour progression, metastasis and poor prognosis (Liu et al, 2003;Adjei, 2005;Wang et al, 2006) and accordingly are expected to increase in tumours. LDH was found to increase in the serum of various malignancies and has been identified as the main recurrent adverse prognostic factors (Schneider, 2006;Duffy and Crown, 2008;Culine, 2009).…”

Section: Discussionmentioning

confidence: 99%

Salivary analysis of oral cancer biomarkers

et al. 2009

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BACKGROUND: Oral cancer is a common and lethal malignancy. Direct contact between saliva and the oral cancer lesion makes measurement of tumour markers in saliva an attractive alternative to serum testing. METHODS: We tested 19 tongue cancer patients, measuring the levels of 8 salivary markers related to oxidative stress, DNA repair, carcinogenesis, metastasis and cellular proliferation and death. RESULTS: Five markers increased in cancer patients by 39 -246%: carbonyls, lactate dehydrogenase, metalloproteinase-9 (MMP-9), Ki67 and Cyclin D1 (CycD1) (Pp0.01). Three markers decreased by 16 -29%: 8-oxoguanine DNA glycosylase, phosphorylated-Src and mammary serine protease inhibitor (Maspin) (Pp0.01). Increase in salivary carbonyls was profound (by 246%, P ¼ 0.012); alterations in CycD1 (87% increase, P ¼ 0.000006) and Maspin (29% decrease, P ¼ 0.007) were especially significant. Sensitivity values of these eight analysed markers ranged from 58% to 100%; specificity values ranged from 42% to 100%. Both values were especially high for the CycD1 and Maspin markers, 100% for each value of each marker. These were also high for carbonyls, 90% and 80%, respectively, and for MMP-9, 100% and 79%, respectively. CONCLUSIONS: The significance of each salivary alteration is discussed. As all alterations correlated with each other, they may belong to a single carcinogenetic network. Cancer-related changes in salivary tumour markers may be used as a diagnostic tool for diagnosis, prognosis and post-operative monitoring.

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“…The inhibition of ERK1/2 phosphorylation has been shown to impact on the levels and activity of cell cycle proteins, in particular cyclins [29,30]. MAPK cascades drive specific cell cycle responses to extracellular stimuli, at least in part, through the modulation of cyclin D1 expression [29,30].…”

Section: Erk1/2 Activity and Cyclin D1 Expressionmentioning

confidence: 99%

“…MAPK cascades drive specific cell cycle responses to extracellular stimuli, at least in part, through the modulation of cyclin D1 expression [29,30]. Indeed, the expression of cyclin D1 has been shown to be positively regulated by MEK -ERK signalling, indicating that ERK activation is required for cyclin D1 expression [29].…”

Section: Erk1/2 Activity and Cyclin D1 Expressionmentioning

confidence: 99%

Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1

Corona

Deiana

Incani

et al. 2009

Molecular Nutrition Food Res

121

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Extra virgin olive oil is rich in phenolic compounds which are believed to exert beneficial effects against many pathological processes, including the development of colon cancer. We show that one of the major polyphenolic constituents of extra virgin olive oil, hydroxytyrosol (HT), exerts strong antiproliferative effects against human colon adenocarcinoma cells via its ability to induce a cell cycle block in G2/M. These antiproliferative effects were preceded by a strong inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation and a downstream reduction of cyclin D1 expression, rather than by inhibition of p38 activity and cyclooxygenase-2 (COX-2) expression. These findings are of particular relevance due to the high colonic concentration of HT compared to the other olive oil polyphenols and may help explain the inverse link between colon cancer and olive oil consumption.

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Activation of ERK1/2 and cyclin D1 expression in oral tongue squamous cell carcinomas: Relationship between clinicopathological appearances and cell proliferation

Cited by 45 publications

References 31 publications

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

Salivary analysis of oral cancer biomarkers

Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1

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