Heat shock protein 20 (HSPB6) regulates TNF-α-induced intracellular signaling pathway in human hepatocellular carcinoma cells

Nagasawa, Takayuki; Matsushima‐Nishiwaki, Rie; Yasuda, Eisuke; Matsuura, Junya; Toyoda, Hidenori; Kikuchi, Yuji; Kumada, Takashi; Kozawa, Osamu

doi:10.1016/j.abb.2014.10.010

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…HSPB6 reportedly inhibited the proliferation of HCC cells via suppression of the MAPK family, including JNK and the PI3K/Akt pathway [84,85]. Furthermore, in consistent with the previous result that HSPB6 inhibited LPS-induced NF-κB activation in cardiomyocytes, HSPB6 acts as a negative regulator of HCC via down-regulation of TNF-α-stimulated IKK/IκB/NF-κB pathway [86]. Additionally, HSPB6 directly associated with Bax, whereby it stimulated caspase cascade and induced apoptosis in HCC [11].…”

Section: Role Of Hspb6 In Cancersupporting

confidence: 75%

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

Xiao

Zhou

et al. 2017

Cell Physiol Biochem

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HSPB6(Heat shock protein B6), is also referred to as P20/HSP20. Unlike other many other members of sHSP(small Heat shock protein) family, which tend to form high-molecular-mass oligomers, in solution, human HSPB6 only forms dimers. However, it still exhibits chaperon-like activity comparable with that of HSPB5. It is expressed ubiquitously, with high and constitutive expression in muscular tissues. sHSPs characteristically function as molecular chaperones and HSPB6 also has a molecular chaperone activity. HSPB6 is up-regulated in response to diverse cellular stress or damage and protect cells from otherwise lethal conditions. HSPB6 is widely recognized as a principle mediator of cardioprotective signaling and recent studies have unraveled the protective role of HSPB6 in disease or injury to the central nervous system. Moreover, accumulating evidence has implicated HSPB6 as a key mediator of diverse vital physiological processes, such as smooth muscle relaxation, platelet aggregation. The versatility of HSPB6 can be explained by its direct involvement in regulating different client proteins and its ability to form heterooligomer with other sHSPs, which seems to be dependent on HSPB6 phosphorylation. This review focuses on the properties including expression and regulation pattern, phosphorylation, chaperon activity, multiple cellular targets of HSPB6, as well as its possible role in physical and pathological conditions.

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Section: Role Of Hspb6 In Cancersupporting

confidence: 75%

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

Xiao

Zhou

et al. 2017

Cell Physiol Biochem

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“…Expression of HSP20 was inversely correlated with tumor progression in patients with ovarian cancer [ 40 ]. Upregulation of HSP20 in human hepatocellular carcinoma cells can inhibit cell proliferation via suppression of the AKT signaling pathway [ 42 ], inhibit TGFα-induced migration and invasion via suppression of the JNK signaling pathway [ 37 ], and stimulate the caspase cascade through direct association with Bax [ 41 ]; HSP20 upregulation also suppresses hepatocellular carcinoma progression by downregulating TNFα-stimulated intracellular signaling [ 38 ]. Downregulation of HSP20 was observed in colorectal cancer specimens compared with their paired normal tissues and was related to advanced TNM stage, lymph node metastasis, and tumor recurrence [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China

et al. 2018

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BackgroundAberrant DNA methylation occurs frequently in cancer. The aim of this study was to identify novel methylation markers in lung cancer in Xuanwei, China, through integrated genome-wide DNA methylation and gene expression studies.MethodsDifferentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected on 10 paired lung cancer tissues and noncancerous lung tissues by methylated DNA immunoprecipitation combined with microarray (MeDIP-chip) and gene expression microarray analyses, respectively. Integrated analysis of DMRs and DEGs was performed to screen out candidate methylation-related genes. Both methylation and expression changes of the candidate genes were further validated and analyzed.ResultsCompared with normal lung tissues, lung cancer tissues expressed a total of 6,899 DMRs, including 5,788 hypermethylated regions and 1,111 hypomethylated regions. Integrated analysis of DMRs and DEGs identified 45 tumor-specific candidate genes: 38 genes whose DMRs were hypermethylated and expression was downregulated, and 7 genes whose DMRs were hypomethylated and expression was upregulated. The methylation and expression validation results identified 4 candidate genes (STXBP6, BCL6B, FZD10, and HSPB6) that were significantly hypermethylated and downregulated in most of the tumor tissues compared with the noncancerous lung tissues.ConclusionsThis integrated analysis of genome-wide DNA methylation and gene expression in lung cancer in Xuanwei revealed several genes regulated by promoter methylation that have not been described in lung cancer before. These results provide new insight into the carcinogenesis of lung cancer in Xuanwei and represent promising new diagnostic and therapeutic targets.

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“…The TNM classification records the primary and regional nodal extent of the tumor, and the metastasis. In addition, we showed that HSP20 stimulates apoptosis of HCC cells by direct interaction with Bax, and that HSP20 down-regulates tumor necrosis factor (TNF)-α-stimulated nuclear factor-κB (NF-κB) signaling pathway by suppression of inhibitor κB kinase (IKK)-α expression in human HCC [ 21 , 22 ]. Furthermore, HSP20 reduces TGF-α-stimulated HCC cell growth by suppressing the mitogen-activated protein kinase (MAPK) family, including c-Jun N-terminal kinase (JNK) and the phosphoinositide 3-kinase (PI3K)/AKT pathway [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylated Heat Shock Protein 20 (HSPB6) Regulates Transforming Growth Factor-α-Induced Migration and Invasion of Hepatocellular Carcinoma Cells

et al. 2016

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Human hepatocellular carcinoma (HCC) is one of the major malignancies in the world. Small heat shock proteins (HSPs) are reported to play an important role in the regulation of a variety of cancer cell functions, and the functions of small HSPs are regulated by post-translational modifications such as phosphorylation. We previously reported that protein levels of a small HSP, HSP20 (HSPB6), decrease in vascular invasion positive HCC compared with those in the negative vascular invasion. Therefore, in the present study, we investigated whether HSP20 is implicated in HCC cell migration and the invasion using human HCC-derived HuH7 cells. The transforming growth factor (TGF)-α-induced migration and invasion were suppressed in the wild-type-HSP20 overexpressed cells in which phosphorylated HSP20 was detected. Phospho-mimic-HSP20 overexpression reduced the migration and invasion compared with unphosphorylated HSP20 overexpression. Dibutyryl cAMP, which enhanced the phosphorylation of wild-type-HSP20, significantly reduced the TGF-α-induced cell migration of wild-type HSP20 overexpressed cells. The TGF-α-induced cell migration was inhibited by SP600125, a c-Jun N-terminal kinases (JNK) inhibitor. In phospho-mimic-HSP20 overexpressed HuH7 cells, TGF-α-stimulated JNK phosphorylation was suppressed compared with the unphosphorylated HSP20 overexpressed cells. Moreover, the level of phospho-HSP20 protein in human HCC tissues was significantly correlated with tumor invasion. Taken together, our findings strongly suggest that phosphorylated HSP20 inhibits TGF-α-induced HCC cell migration and invasion via suppression of the JNK signaling pathway.

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Heat shock protein 20 (HSPB6) regulates TNF-α-induced intracellular signaling pathway in human hepatocellular carcinoma cells

Cited by 12 publications

References 30 publications

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China

Phosphorylated Heat Shock Protein 20 (HSPB6) Regulates Transforming Growth Factor-α-Induced Migration and Invasion of Hepatocellular Carcinoma Cells

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