Expression patterns of the tumor suppressor PDCD4 and correlation with β-catenin expression in gastric cancers

Kakimoto, Takashi; Shiraishi, Ryosuke; Iwakiri, Ryuichi; Fujimoto, Kazuma; Takahashi, Hirokazu; Hamajima, Hiroshi; Mizuta, Toshihiko; Ideguchi, H; Toda, Shuji; Kitajima, Yoshihiko; Ozaki, Iwata; Matsuhashi, Sachiko

doi:10.3892/or.2011.1450

Cited by 9 publications

(8 citation statements)

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“…Different ORs and 95% CIs were obtained for the assessment of clinical stage and OS. A similar situation was observed in the study by Kakimoto et al [50] that examined the association between PDCD4 expression and histological differentiation. These findings suggest that the prognostic value of PDCD4 in human malignancies should be studied by further stratified analysis, including the determination of precise cellular localization of PDCD4.…”

Section: Discussionsupporting

confidence: 82%

“…a Forest plot shows that low PDCD4 expression is significantly associated with moderate/poor differentiation of digestive system cancers and head and neck cancers. Two sites of PDCD4 expression were reported by Kakimoto et al: Kakimoto [50] (01) for PDCD4 expression in nucleus and Kakimoto [50] (02) for PDCD4 expression in cytoplasm of gastric cancer cells. Two sites of PDCD4 expression were reported by Nagao et al: Nagao [15] (01) for PDCD4 expression in nucleus and Nagao [15] (02) for PDCD4 expression in cytoplasm of pancreatic cancer cells.…”

Section: Resultsmentioning

confidence: 99%

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The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis

Gao

et al. 2016

Chin J Cancer

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BackgroundProgrammed cell death protein 4 (PDCD4) is a novel tumor suppressor protein involved in programmed cell death. Its association with cancer progression has been observed in multiple tumor models, but evidence supporting its association with solid tumors in humans remains controversial. This study aimed to determine the clinical significance and prognostic value of PDCD4 in solid tumors.MethodsA systematic literature review was performed to retrieve publications with available clinical information and survival data. The eligibility of the selected articles was based on the criteria of the Dutch Cochrane Centre proposed by the Meta-analysis Of Observational Studies in Epidemiology group. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) for survival analysis were calculated. Publication bias was examined by Begg’s and Egger’s tests.ResultsClinical data of 2227 cancer patients with solid tumors from 23 studies were evaluated. PDCD4 expression was significantly associated with the differentiation status of head and neck cancer (OR 4.25, 95% CI 1.87–9.66) and digestive system cancer (OR 2.87, 95% CI 1.84–4.48). Down-regulation of PDCD4 was significantly associated with short overall survival of patients with head and neck (HR: 3.44, 95% CI 2.38–4.98), breast (HR: 1.86, 95% CI 1.36–2.54), digestive system (HR: 2.12, 95% CI 1.75–2.56), and urinary system cancers (HR: 3.16, 95% CI 1.06–9.41).ConclusionsThe current evidence suggests that PDCD4 down-regulation is involved in the progression of several types of solid tumor and is a potential marker for solid tumor prognoses. Its clinical usefulness should be confirmed by large-scale prospective studies.

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis

Gao

et al. 2016

Chin J Cancer

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“…PDCD4 expresses ubiquitously in the tissues and the protein is localized in the nuclei or cytoplasm or in both depending on the cell types. The expression of PDCD4-protein is often down-regulated in the tumors [17,18,19,20] but is maintained in high levels in a large number of tumors.…”

Section: Introductionmentioning

confidence: 99%

Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions

Matsuhashi

Manirujjaman

Hamajima

et al. 2019

IJMS

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111

118

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PDCD4 is a novel tumor suppressor to show multi-functions inhibiting cell growth, tumor invasion, metastasis, and inducing apoptosis. PDCD4 protein binds to the translation initiation factor eIF4A, some transcription factors, and many other factors and modulates the function of the binding partners. PDCD4 downregulation stimulates and PDCD4 upregulation inhibits the TPA-induced transformation of cells. However, PDCD4 gene mutations have not been found in tumor cells but gene expression was post transcriptionally downregulated by micro environmental factors such as growth factors and interleukins. In this review, we focus on the suppression mechanisms of PDCD4 protein that is induced by the tumor promotors EGF and TPA, and in the inflammatory conditions. PDCD4-protein is phosphorylated at 2 serines in the SCFβTRCP ubiquitin ligase binding sequences via EGF and/or TPA induced signaling pathway, ubiquitinated, by the ubiquitin ligase and degraded in the proteasome system. The PDCD4 protein synthesis is inhibited by microRNAs including miR21.

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“…In addition, the expression level of miR-21 was associated with progression-related factors, such as depth of tumour invasion (Ueda et al , 2010). In addition, PDCD4 is strongly expressed in the nuclei of normal gastric mucosal cells, whereas it is expressed at lower levels in the gastric adenocarcinoma (Kakimoto et al , 2011). Low PDCD4 expression was significantly correlated with poor clinical prognosis (Motoyama et al , 2010).…”

mentioning

confidence: 99%

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence

et al. 2013

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Background:Multiple early gastric cancers (EGCs) may develop in 6–14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence.Methods:Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed.Results:The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71–83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30–18.8).Conclusion:CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

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Expression patterns of the tumor suppressor PDCD4 and correlation with β-catenin expression in gastric cancers

Cited by 9 publications

References 41 publications

The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis

The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis

Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence

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