Hic‐5 affects proliferation, migration and invasion of B16 murine melanoma cells

Noguchi, Fumihito; Inui, Shigeki; Nakajima, Takeshi; Itami, Satoshi

doi:10.1111/pcmr.12005

Cited by 14 publications

(16 citation statements)

References 36 publications

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“…Furthermore, ectopic expression of Hic-5 is sufficient to promote normal mammary cells to undergo EMT [ 27 ]. In addition, the melanoma cell depleted of Hic-5 exhibit decreased cell motility and metastatic activity in vivo [ 28 ]. One recent report demonstrated the upregulation of Hic-5 in HCCs overexpressing proline-rich tyrosine kinase 2 (Pyk2) [ 29 ], which is known to be involved in HCC metastasis [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression

You

et al. 2015

Oncotarget

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One of the signaling components involved in hepatocellular carcinoma (HCC) progression is the focal adhesion adaptor paxillin. Hydrogen peroxide inducible clone-5 (Hic-5), one of the paralogs of paxillin, exhibits many biological functions distinct from paxillin, but may cooperate with paxillin to trigger tumor progression. Screening of Hic-5 in 145 surgical HCCs demonstrated overexpression of Hic-5 correlated well with intra- and extra-hepatic metastasis. Hic-5 highly expressed in the patient derived HCCs with high motility such as HCC329 and HCC353 but not in the HCCs with low motility such as HCC340. Blockade of Hic-5 expression prevented constitutive migration of HCC329 and HCC353 and HGF-induced cell migration of HCC340. HCC329Hic-5(−), HCC353Hic-5(−), HCC372Hic-5(−), the HCCs stably depleted of Hic-5, exhibited reduced motility compared with each HCC expressing Scramble shRNA. Moreover, intra/extrahepatic metastasis of HCC329Hic-5(−) in SCID mice greatly decreased compared with HCC329Scramble. On the other hand, ectopic Hic-5 expression in HCC340 promoted its progression. Constitutive and HGF-induced Hic-5 expression in HCCs were suppressed by the reactive oxygen species (ROS) scavengers catalase and dithiotheritol and c-Jun N-terminal kinase (JNK) inhibitor SP600125. On the contrary, depletion of Hic-5 blocked constitutive and HGF-induced ROS generation and JNK phosphorylation in HCCs. Also, ectopic expression of Hic-5 enhanced ROS generation and JNK phosphorylation. These highlighted that Hic-5 plays a central role in the positive feedback ROS-JNK signal cascade. Finally, the Chinese herbal derived anti-HCC peptide LZ-8 suppressed constitutive Hic-5 expression and JNK phosphorylation. In conclusion, Hic-5 mediates ROS-JNK signaling and may serve as a therapeutic target for prevention of HCC progression.

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Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression

You

et al. 2015

Oncotarget

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“…Immunoblotting was performed as previously described (33). Antibodies used were: mouse monoclonal anti-ATP synthase beta IgG (1:10,000; 612518, BD Biosciences), rabbit polyclonal anti-PGC-1 IgG (1:200; sc-13067, Santa Cruz Biotechnology), rabbit polyclonal anti-cleaved caspase-3 p11 IgG (1:200; sc-22171-R, Santa Cruz Biotechnology), rabbit polyclonal anti-cleaved caspase-6 (Asp162) IgG (1:1,000; #9761, Cell Signaling Technology), and anti-b-actin (1:20,000; A5441, Sigma-Aldrich).…”

Section: Western Blottingmentioning

confidence: 99%

Calcium-Dependent Enhancement by Extracellular Acidity of the Cytotoxicity of Mitochondrial Inhibitors against Melanoma

Noguchi

Inui

Fedele

et al. 2017

Molecular Cancer Therapeutics

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Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Because acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations, and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH, and systemic alkalinization with NaHCO enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin. Intracellular calcium (Ca) was significantly increased in melanoma cells treated with mitochondrial inhibitors at an acidic extracellular pH and an intracellular Ca chelator, BAPTA/AM, inhibited cytoplasmic Ca as well as melanoma cell death. Surprisingly, ROS scavengers synergized with increased apoptosis in cells treated with mitochondrial inhibitors, suggesting that ROS contributes to cell survival in this context. Notably, the cytotoxic enhancement of mitochondrial inhibitors by acidity was distinct from PGC1alpha-driven mitochondrial addiction, from therapy-induced senescence, and from slow, JARID1B-high-associated cell cycling, all of which have been shown to promote vulnerability to mitochondrial inhibition. These data indicate that extracellular pH profoundly modulates the cytotoxicity of mitochondrial inhibitors against cancer cells. .

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“…In the cytosol, it acts as a scaffold at focal adhesions and controls important cellular processes such as proliferation, invasion, and apoptosis (25)(26)(27). In the nucleus, we and others have shown that it functions as a nuclear receptor coactivator in transient reporter gene assays (24,28).…”

Section: Significancementioning

confidence: 99%

Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid receptor genome occupancy in a gene-selective manner

Chodankar

Schiller

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Ligand activation and DNA-binding dictate the outcome of glucocorticoid receptor (GR)-mediated transcriptional regulation by inducing diverse receptor conformations that interact differentially with coregulators. GR recruits many coregulators via the well-characterized AF2 interaction surface in the GR ligand-binding domain, but Lin11, Isl-1, Mec-3 (LIM) domain coregulator Hic-5 (TGFB1I1) binds to the relatively uncharacterized tau2 activation domain in the hinge region of GR. Requirement of hydrogen peroxide-inducible clone-5 (Hic-5) for glucocorticoid-regulated gene expression was defined by Hic-5 depletion and global geneexpression analysis. Hic-5 depletion selectively affected both activation and repression of GR target genes, and Hic-5 served as an on/ off switch for glucocorticoid regulation of many genes. For some hormone-induced genes, Hic-5 facilitated recruitment of Mediator complex. In contrast, many genes were not regulated by glucocorticoid until Hic-5 was depleted. On these genes Hic-5 prevented GR occupancy and chromatin remodeling and thereby inhibited their hormone-dependent regulation. Transcription factor binding to genomic sites is highly variable among different cell types; Hic-5 represents an alternative mechanism for regulating transcription factor-binding site selection that could apply both within a given cell type and among different cell types. Thus, Hic-5 is a versatile coregulator that acts by multiple genespecific mechanisms that influence genomic occupancy of GR as well transcription complex assembly.nuclear receptor | steroid receptor | enhancer

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Hic‐5 affects proliferation, migration and invasion of B16 murine melanoma cells

Cited by 14 publications

References 36 publications

Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression

Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression

Calcium-Dependent Enhancement by Extracellular Acidity of the Cytotoxicity of Mitochondrial Inhibitors against Melanoma

Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid receptor genome occupancy in a gene-selective manner

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