Clinicopathologic significance and function of mammalian target of rapamycin activation in esophageal squamous cell carcinoma

Kim, Seok-Hyung; Chau, Gia Cac; Jang, Younghoon; Lee, Seung Im; Pyo, Suhkneung; Um, Sung Hee

doi:10.1016/j.humpath.2012.05.011

Cited by 14 publications

(19 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the process of culturing esophageal squamous epithelial cells, the dominant negative mastermind-like 1 (DNMAML1), an inhibitor of Notch signaling pathway, activates CCND1 expression and promotes the development of cell hyperplasia [10]. A study of 165 esophageal cancer specimens showed that the increased phosphorylation level of the mammalian target of rapamycin (mTOR) signal protein was related to CCND1 overexpression, which affected cancer cell proliferation, metastasis and invasion [22]. Another study of 181 esophageal cancer surgical specimens revealed that the positive expression rate for CCND1 was 37.6% and gradually increased with the decreased degree of cancer cell differentiation, suggesting that there is a certain correlation between CCND1 and cancer cell differentiation [23].…”

Section: Discussionmentioning

confidence: 99%

“…However, studies of the upstream regulatory factors and the direct activating mechanism for CCND1 overexpression in cancer cells have rarely been reported and many questions remain to be elucidated. It is already known that the activation of the EGFR, Notch, c-myc, Wnt2/β-catenin, AKT, and mTOR signaling pathways is associated with CCND1 expression in cancer cells [9,10,22,26]. There are many regulatory factors involved in these pathways; most of the factors have an indirect effect on CCND1 expression, and the upstream genes or factors that directly regulate CCND1 expression remain unclear.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma

et al. 2014

Cancer Letters

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma

et al. 2014

Cancer Letters

View full text Add to dashboard Cite

“…samplesMean age (Years)Genders (Male/Female)NIT (Yes/No)StagesCP featuresPrognosisTotalPENEBoone et al (2008) [38]EnglishNetherlandROS1989–20067 ✓ ✗ 105267962.056/49NoneI-IVChen et al (2010) [39]ChineseChina mainlandROS2006–20077 ✓ ✗ 623329NININoneNIChuang et al (2015) [40]EnglishTaiwanROSNI8 ✓ ✓ 75393657.072/354/21I-IVHirashima et al (2010) [41]EnglishJapanROS1996–20069 ✓ ✓ 143717263.8126/17NoneI-IIIHou et al (2014) [42]EnglishChina mainlandROSNI7 ✓ ✗ 35221361.316/19NoneI-IVKim et al (2013) [43]EnglishKoreaROS1995–20088 ✓ ✓ 1657491NI159/6NoneI-IVLi et al (2012) [44]EnglishTaiwanROS1999–20099 ✗ ✓ 77443352.075/2All receivedI-IIILi et al (2015) [45]EnglishTaiwanROSNI8 ✓ ✓ 105594654.01...…”

Section: Resultsmentioning

confidence: 99%

“…This meta-analysis involved a total of 915 ESCC cases, including 502 Chinese patients from China mainland and Taiwan region (ratio = 54.9 %) [39, 40, 42, 44–46], 165 patients from Korea (ratio = 18.0 %) [43], 143 patients from Japan (ratio = 15.6 %) [41] and 105 patients from Netherland (ratio = 11.5 %) [38]. All of these patients were consecutively enrolled from 1989 to 2012.…”

Section: Resultsmentioning

confidence: 99%

Clinicopathological and prognostic significance of mTOR and phosphorylated mTOR expression in patients with esophageal squamous cell carcinoma: a systematic review and meta-analysis

Wang

Huang

et al. 2016

BMC Cancer

View full text Add to dashboard Cite

BackgroundMammalian target of rapamycin (mTOR) is a serine/threonine protein kinase responsible for regulating ribosomal biogenesis and protein synthesis. Dysregulation of mTOR contributes to tumorigenesis, angiogenesis, cellular growth and metastasis but its roles in esophageal squamous cell carcinoma (ESCC) are controversial. Therefore, the objective of this study is to evaluate the prognostic and clinicopathological significance of mTOR/p-mTOR expression in ESCC.MethodsLiterature retrieval was conducted by searching PubMed, EMBASE and the Web of Science for full-text papers that met our eligibility criteria. Odds ratio (OR) and hazard ratio (HR) with 95 % confidence interval (CI) served as the appropriate summarized statistics for assessments of clinicopathological and prognostic significance, respectively. Cochrane Q-test and I2-statistic were adopted to estimate the heterogeneity level between studies. Potential publication bias was detected by Begg’s test and Egger’s test.ResultsA total of 915 ESCC patients from nine original articles were included into this meta-analysis. The pooled analyses suggested that mTOR/p-mTOR expression was significantly correlated with the unfavorable outcomes of differentiation degree (OR: 2.63; 95 % CI: 1.71–4.05; P = 0.001), tumor invasion (OR: 1.48; 95 % CI: 1.02–2.13; P = 0.037), TNM stage (OR: 2.25; 95 % CI: 1.05–4.82; P = 0.037) and lymph node metastasis (OR: 1.82; 95 % CI: 1.06–3.11; P = 0.029), but had no significant relationship to the genders (OR: 0.81; 95 % CI: 0.50–1.32; P = 0.396). Moreover, mTOR/p-mTOR expression could independently predict the worse overall survival (HR: 2.04; 95 % CI: 1.58–2.62; P < 0.001), disease-free survival (HR: 2.39; 95 % CI: 1.64–3.49; P < 0.001) and cancer-specific survival (HR: 1.62; 95 % CI: 1.18–2.23; P = 0.003) of patients with ESCC. Such prognostic value of mTOR was not substantially altered by further subgroup analyses.ConclusionsPositive expression of mTOR and p-mTOR was significantly associated with the unfavorable conditions on the depth of tumor invasion, TNM stage, differentiation degree and lymph node metastasis. mTOR and p-mTOR could serve as a valuable predictor for the poor prognosis of ESCC. More high-quality worldwide studies performing a multivariate analysis based on larger sample size are urgently required for further verifying and modifying our findings in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2940-7) contains supplementary material, which is available to authorized users.

show abstract

“…In early stage, triple negative (estrogen and progesteron receptor, Her2 amplification) breast carcinomas, phosphorylated mTOR expression significantly correlated with worse overall survival and recurrence-free survival [29]. In oesophageal squamous cell carcinoma, high levels of phosphorylated mTOR were significantly associated with shortened disease specific survival and mTOR expression remained an independent adverse prognostic factor in multivariate analysis [30]. Similar data were obtained in early stage Non Small Cell Lung Cancer where angioinvasion and mTOR expression were significant predictors of poor survival at both univariate and multivariate analysis [31].…”

Section: Discussionmentioning

confidence: 99%

mTOR pathway activation in multiple myeloma cell lines and primary tumour cells: pomalidomide enhances cytoplasmic-nuclear shuttling of mTOR protein

et al. 2015

View full text Add to dashboard Cite

mTOR is a protein kinase that plays a central role in regulating critical cellular processes. We evaluated the activation and cellular localization of the mTOR pathway in multiple myeloma (MM) and analyzed the role of pomalidomide in regulating mTOR. By immunohistochemistry cytoplasmic p-mTOR stained positive in 57 out 101 (57.6%) cases with a nuclear p-mTOR localization in 14 out 101 samples (13.8%). In the 70 MM samples analyzed for the entire pathway, p-mTOR expression significantly correlated with p-AKT, p-P70S6K, and p-4E-BP1 suggesting that the AKT/mTOR pathway is activated in a subset of MM patients. Immunofluorescence assays demonstrated that mTOR protein is distributed throughout the cytoplasm and the nucleus at baseline in MM cell lines and in plasma cells of 13 MM patients and that pomalidomide facilitated the shift of the mTOR protein in the nucleus. By western blotting, treatment with pomalidomide increased nuclear mTOR and p-mTOR expression levels in the nucleus with a concomitant decrease of the cytoplasmic fractions while does not seem to affect significantly AKT phosphorylation status. In MM cells the anti-myeloma activity of pomalidomide may be mediated by the regulation of the mTOR pathway.

show abstract

Clinicopathologic significance and function of mammalian target of rapamycin activation in esophageal squamous cell carcinoma

Cited by 14 publications

References 24 publications

Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma

Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma

Clinicopathological and prognostic significance of mTOR and phosphorylated mTOR expression in patients with esophageal squamous cell carcinoma: a systematic review and meta-analysis

mTOR pathway activation in multiple myeloma cell lines and primary tumour cells: pomalidomide enhances cytoplasmic-nuclear shuttling of mTOR protein

Contact Info

Product

Resources

About