The combination of silencing BAG3 and inhibition of the JNK pathway enhances hyperthermia sensitivity in human oral squamous cell carcinoma cells

Yunoki, Tatsuya; Kariya, Ayako; Kondo, Takashi; Hayashi, Atsushi; Tabuchi, Yoshiaki

doi:10.1016/j.canlet.2013.01.049

Cited by 24 publications

(21 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another gene implicated in SZ on a molecular level that was significantly affected by HS was BAG3 , which codes for an HSP70 co-chaperone that mediates adaptive responses to stressful stimuli [75], [129], [130]. It has been found to be differentially expressed in the prefrontal cortex of patients with SZ, and in neurons derived from SZ-specific iPSCs [131], [132].…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon

et al. 2014

View full text Add to dashboard Cite

Schizophrenia (SZ) and autism spectrum disorders (ASD) are highly heritable neuropsychiatric disorders, although environmental factors, such as maternal immune activation (MIA), play a role as well. Cytokines mediate the effects of MIA on neurogenesis and behavior in animal models. However, MIA stimulators can also induce a febrile reaction, which could have independent effects on neurogenesis through heat shock (HS)-regulated cellular stress pathways. However, this has not been well-studied. To help understand the role of fever in MIA, we used a recently described model of human brain development in which induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional neuronal aggregates that resemble a first trimester telencephalon. RNA-seq was carried out on aggregates that were heat shocked at 39°C for 24 hours, along with their control partners maintained at 37°C. 186 genes showed significant differences in expression following HS (p<0.05), including known HS-inducible genes, as expected, as well as those coding for NGFR and a number of SZ and ASD candidates, including SMARCA2, DPP10, ARNT2, AHI1 and ZNF804A. The degree to which the expression of these genes decrease or increase during HS is similar to that found in copy loss and copy gain copy number variants (CNVs), although the effects of HS are likely to be transient. The dramatic effect on the expression of some SZ and ASD genes places HS, and perhaps other cellular stressors, into a common conceptual framework with disease-causing genetic variants. The findings also suggest that some candidate genes that are assumed to have a relatively limited impact on SZ and ASD pathogenesis based on a small number of positive genetic findings, such as SMARCA2 and ARNT2, may in fact have a much more substantial role in these disorders - as targets of common environmental stressors.

show abstract

Section: Discussionmentioning

confidence: 99%

Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Gross et al (27) observed that inhibition of c-Jun with SP600125 suppresses the growth of HNSCC cells. In addition, Yunoki et al (28) proposed that combined silencing of B-cell lymphoma 2-associated athanogene 3 (a co-chaperone of heat shock protein 70) and inhibition of the JNK signaling pathway may be an option in hyperthermia therapy in OSCC. However, several studies highlighted the role of activated JNK in apoptosis and tumor suppression in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

“…c-Jun N-terminal kinases (JNKs) are members of the MAPK family, and become activated by a stressful cellular environment, including ultraviolet irradiation, oxidative stress, changes in osmolarity or metabolism, DNA damage, heat shock and inflammatory cytokine signaling (25). JNK signaling has been studied in HNSCC with controversial findings; thus, while certain studies support a pro-oncogenic function of JNK, others provide evidence that JNKs act as tumor suppressors in HNSCC (26)(27)(28).…”

Section: Jnk1/2 Expression and Modulation Of Stat3 Signaling In Oral mentioning

confidence: 99%

JNK1/2 expression and modulation of STAT3 signaling in oral cancer

et al. 2016

View full text Add to dashboard Cite

Abstract. Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that link extracellular stimuli with intracellular responses and participate in numerous cellular processes such as growth, proliferation, differentiation, inflammation and apoptosis. Persistent activation of signal transducer and activator of transcription 3 (STAT3), which is accompanied by increases in STAT3 tyrosine phosphorylation, is associated with cell proliferation, differentiation and apoptosis in oral squamous cell carcinoma (OSCC). The role and significance of the activation of MAPKs, particularly of c-Jun N-terminal kinase (JNK), on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examines the effects of JNK1/2 modulation on STAT3 signaling and cellular activities in OSCC cells. The expression levels of STAT3 [total, tyrosine phosphorylated (p-Tyr) and serine phosphorylated (p-Ser)], JNK, c-Jun and cyclin D1 were assessed in the OSCC cell lines SCC25 and SCC9. Inhibition of JNK1/2 was achieved by pharmacological agents (SP600125) and by small interfering RNA (siRNA) silencing, while JNK1/2 was induced by active MAPK kinase 7. Cell proliferation and viability rates were also evaluated. Inhibition of JNK1/2 with either SP600125 treatment or specific siRNA silencing resulted in decreased levels of p-Ser STAT3 and increased levels of p-Tyr STAT3 and cyclin D1 in both cell lines. Furthermore, JNK1/2 inhibition resulted in a dose-dependent increase in cell growth and viability in both cell lines. Opposite results were observed with JNK1/2 induction in both cell lines. The present results are supportive of a potential tumor suppressive role of JNK1/2 signaling in OSCC, which may be mediated through negative crosstalk with the oncogenic STAT3 signaling pathway. The possible therapeutic implications of JNK1/2 inhibition for patients with OSCC require to be investigated.

show abstract

“…For measuring chromatin condensation, a Nuclear-ID™ Green Chromatin Condensation Kit (Enzo Life Sciences Inc., Farmingdale, NY, USA) was used. Finally, the stained samples were run on an Epics XL flow cytometer (Beckman Coulter Inc., Brea, CA, USA) [55]. …”

Section: Methodsmentioning

confidence: 99%

“…The siRNAs were synthesized by Nippon Gene Co., Ltd. (Toyama, Japan) (Table S6). Luciferase siRNA was used as a negative control siRNA [55]. …”

Section: Methodsmentioning

confidence: 99%

Genes and Gene Networks Involved in Sodium Fluoride-Elicited Cell Death Accompanying Endoplasmic Reticulum Stress in Oral Epithelial Cells

Tabuchi

Yunoki

Hoshi

et al. 2014

IJMS

Self Cite

View full text Add to dashboard Cite

Here, to understand the molecular mechanisms underlying cell death induced by sodium fluoride (NaF), we analyzed gene expression patterns in rat oral epithelial ROE2 cells exposed to NaF using global-scale microarrays and bioinformatics tools. A relatively high concentration of NaF (2 mM) induced cell death concomitant with decreases in mitochondrial membrane potential, chromatin condensation and caspase-3 activation. Using 980 probe sets, we identified 432 up-regulated and 548 down-regulated genes, that were differentially expressed by >2.5-fold in the cells treated with 2 mM of NaF and categorized them into 4 groups by K-means clustering. Ingenuity® pathway analysis revealed several gene networks from gene clusters. The gene networks Up-I and Up-II included many up-regulated genes that were mainly associated with the biological function of induction or prevention of cell death, respectively, such as Atf3, Ddit3 and Fos (for Up-I) and Atf4 and Hspa5 (for Up-II). Interestingly, knockdown of Ddit3 and Hspa5 significantly increased and decreased the number of viable cells, respectively. Moreover, several endoplasmic reticulum (ER) stress-related genes including, Ddit3, Atf4 and Hapa5, were observed in these gene networks. These findings will provide further insight into the molecular mechanisms of NaF-induced cell death accompanying ER stress in oral epithelial cells.

show abstract

The combination of silencing BAG3 and inhibition of the JNK pathway enhances hyperthermia sensitivity in human oral squamous cell carcinoma cells

Cited by 24 publications

References 46 publications

Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon

Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon

JNK1/2 expression and modulation of STAT3 signaling in oral cancer

Genes and Gene Networks Involved in Sodium Fluoride-Elicited Cell Death Accompanying Endoplasmic Reticulum Stress in Oral Epithelial Cells

Contact Info

Product

Resources

About