FOXO6 promotes gastric cancer cell tumorigenicity via upregulation of C‐myc

Li, Qinyu; Cui, Long; Du, Zhimin; Shi, Minmin; Wu, Wenjun; Yang, Weiping; Peng, Chenghong

doi:10.1016/j.febslet.2013.05.027

Cited by 34 publications

(29 citation statements)

References 34 publications

(36 reference statements)

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“…Recent studies have suggested that FOXO6 is involved in the carcinogenesis of certain malignancies, including gastric cancer,19 hepatocellular carcinoma20 and lung cancer 21. However, no currently available evidence exists regarding the role of FOXO4 and FOXO6 in TNBC.…”

Section: Discussionmentioning

confidence: 99%

FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in triple-negative breast cancer

Rehman

Kim

et al. 2018

J Clin Pathol

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AimsForkhead box O (FOXO) transcription factors, consisting of FOXO1, FOXO3a, FOXO4 and FOXO6, are involved in carcinogenesis and tumour progression. Recent studies have suggested that FOXOs act as tumour suppressors in a variety of human cancers. This study investigated the clinicopathological significance of FOXOs in triple-negative breast cancer (TNBC).MethodsFOXO protein expressions were assessed by immunohistochemistry in 125 TNBC tissues. Correlations between FOXO protein expression and various clinicopathological parameters, including patients’ survival, were investigated. MDA-MB-468 cell line was used for in vitro cell proliferation and migration assay.ResultsFOXO1 protein expression was not observed in all 125 TNBC tissues. FOXO4 and FOXO6 protein expressions were detected in 11 (8.8%) and 14 (11.2%) TNBC tissues, respectively. Loss of FOXO4 expression was significantly associated with high histological grade (P=0.014, χ2 test), and TNBCs with positive FOXO6 expression correlated with high grade (P=0.020, χ2 test). FOXO3a expression was detected in 40 (32%) TNBC cases and correlated with adverse clinicopathological features, such as lymph node metastasis (P=0.021, χ2 test), perineural invasion (P=0.013, χ2 test) and higher Ki-67 proliferation index (P=0.048, t-test). Additionally, FOXO3a expression was significantly associated with poor disease-free survival (P=0.015, log-rank test). In the in vitro study, siRNA-mediated FOXO3a knockdown in the MDA-MB-468 cell line inhibited cell proliferation and migration.ConclusionAmong FOXO members, FOXO3a may have a potential role in promoting tumour cell migration and proliferation and may serve as a prognostic biomarker and a potential therapeutic target for TNBC.

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Section: Discussionmentioning

confidence: 99%

FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in triple-negative breast cancer

Rehman

Kim

et al. 2018

J Clin Pathol

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“…Single and double FoxO knockout mice did not show increased rates of tumorigenesis, but the triple deletion of Foxo1a , Foxo3a and Foxo4 resulted in accelerated tumor progression in adult mice, together with increased intracellular ROS levels [250] . In contrast, a single knockout of the less related FoxO6 resulted in increased cellular proliferation and promoted the development of gastric cancer [251] .…”

Section: Physiological and Pathophysiological Consequences Of Redox (mentioning

confidence: 94%

Redox regulation of FoxO transcription factors

et al. 2015

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Transcription factors of the forkhead box, class O (FoxO) family are important regulators of the cellular stress response and promote the cellular antioxidant defense. On one hand, FoxOs stimulate the transcription of genes coding for antioxidant proteins located in different subcellular compartments, such as in mitochondria (i.e. superoxide dismutase-2, peroxiredoxins 3 and 5) and peroxisomes (catalase), as well as for antioxidant proteins found extracellularly in plasma (e.g., selenoprotein P and ceruloplasmin). On the other hand, reactive oxygen species (ROS) as well as other stressful stimuli that elicit the formation of ROS, may modulate FoxO activity at multiple levels, including posttranslational modifications of FoxOs (such as phosphorylation and acetylation), interaction with coregulators, alterations in FoxO subcellular localization, protein synthesis and stability. Moreover, transcriptional and posttranscriptional control of the expression of genes coding for FoxOs is sensitive to ROS. Here, we review these aspects of FoxO biology focusing on redox regulation of FoxO signaling, and with emphasis on the interplay between ROS and FoxOs under various physiological and pathophysiological conditions. Of particular interest are the dual role played by FoxOs in cancer development and their key role in whole body nutrient homeostasis, modulating metabolic adaptations and/or disturbances in response to low vs. high nutrient intake. Examples discussed here include calorie restriction and starvation as well as adipogenesis, obesity and type 2 diabetes.

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“…This is accompanied by a shift towards a proapoptotic homeostasis with increased expression of bax and decreased expression of bcl2 [199,200]. The induction of oncogenes like cmyc is also interfering with these processes [199,201]. …”

Section: Response To H Pylori In the Gastric Mucosamentioning

confidence: 99%

Helicobacter pylori and Gastric Cancer

Bornschein

Malfertheiner

2014

Dig Dis

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Infection with Helicobacter pylori is established as the major risk factor for gastric cancer development. Damage of the mucosal barrier due to H. pylori-induced inflammation enhances the carcinogenic effect of other risk factors such as salt intake or tobacco smoking. The genetic disposition of both the bacterial strain and the host can increase the potential towards gastric cancer formation. Genetic variance of the bacterial proteins CagA and VacA is associated with a higher gastric cancer risk, as are polymorphisms and epigenetic changes in host gene coding for interleukins (IL1β, IL8), transcription factors (CDX2, RUNX3) and DNA repair enzymes. Application of high-throughput assays for genome-wide assessment of either genetic structural variance or gene expression patterns may lead to a better understanding of the pathobiological background of these processes, including the underlying signaling pathways. Understanding of the stepwise alterations that take place in the transition from chronic atrophic gastritis, via metaplastic changes, to invasive neoplasia is vital to define the ‘point of no return' before which eradication of H. pylori has the potential to prevent gastric cancer. Currently, eradication as preventive strategy is only recommended for high-incidence regions in Asia; large population studies with an adequate follow-up are required to demonstrate the effectiveness of such an approach in Western populations.

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FOXO6 promotes gastric cancer cell tumorigenicity via upregulation of C‐myc

Cited by 34 publications

References 34 publications

FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in triple-negative breast cancer

FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in triple-negative breast cancer

Redox regulation of FoxO transcription factors

Helicobacter pylori and Gastric Cancer

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