Hedgehog signaling pathway and gastric cancer

Katoh, Yuriko; Katoh, Masaru

doi:10.4161/cbt.4.10.2184

Cited by 151 publications

(135 citation statements)

References 52 publications

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“…Chronic persistent infection with Helicobacter pylori leads to chronic atrophic gastritis and gastric cancer (31,32). SHH-dependent parietal cell proliferation is implicated in the gastric mucosal repair during chronic Helicobacter pylori infection (6).…”

Section: Hedgehog Signaling Network In Gastrointestinal Tractmentioning

confidence: 99%

“…In the absence of Hedgehog signaling, Patched family receptors (PTCH1/PTCH and PTCH2) inhibit the Smoothened (SMO) signal transducer (1)(2)(3)(4)(5)(6)(13)(14)(15). SMO inactivation leads to formation of the cytoplasmic GLI degradation complex, in which GLI family members (GLI1, GLI2 and GLI3) are phosphorylated by casein kinase I· (CKI·), glycogen synthase kinase-3ß (GSK3ß) and protein kinase A (PKA) (16,17).…”

mentioning

confidence: 99%

“…Hedgehog signaling plays a key role in a variety of processes, such as embryogenesis, maintenance of adult tissue homeostasis, tissue repair during chronic persistent inflammation, and carcinogenesis (1)(2)(3)(4)(5)(6). Hedgehog family ligands, Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH), undergo autoprocessing and lipid modification to generate mature peptides (7)(8)(9).…”

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confidence: 99%

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Hedgehog signaling pathway and gastrointestinal stem cell signaling network (Review)

Katoh¹,

Katoh²

2006

Int J Mol Med

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125

164

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Section: Hedgehog Signaling Network In Gastrointestinal Tractmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Hedgehog signaling pathway and gastrointestinal stem cell signaling network (Review)

Katoh¹,

Katoh²

2006

Int J Mol Med

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125

164

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“…Gli1 is a transcriptional activator [18] , which induces the expression of numerous target genes that regulates proliferation, differentiation, and extracellular matrix interactions [19,20] . Increasing evidence has demonstrated that the Hh signaling pathway plays an important role in multiple tumor types, for example, basal cell carcinoma [21,22] , pancreatic cancer [23] , colon carcinoma [24] , gastric cancer [25] , small cell lung cancer [26] , prostate cancer [27][28][29] , breast cancer [30,31] , early childhood hepatoblastoma [32] , and esophageal cancers [33] .…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

Lü

Zhao

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the role of Hedgehog (Hh) signaling pathway in the invasion and metastasis of human hepatocellular carcinoma (HCC). Methods: Eighty six HCC tissues samples and HCC cell line Bel-7402 were examined. The protein expression of sonic hedgehog (Shh), nuclear glioma-associated oncogene-1 (Gli1), MMP-9 and p-ERK1/2 in HCC was analyzed using immunohistochemistry and Western blot analysis. Boyden chamber assay and wound-healing assay were used to quantify the invasion and metastasis of Bel-7402 cells. Results: In 86 HCC tissue samples, the positive ratio of Shh and nucleus Gli1 was 67.44% (58/86) and 60.47% (52/86), respectively; the expression of nucleus Gli1 was correlated with the tumor pathological grade (P=0.034), and with the ability of the tumor to invade and metastasize (P=0.001); the expression of nucleus Gli1 was also correlated with p-ERK1/2 (P=0.031) and with MMP-9 (P=0.034). Neither Shh, nor nucleus Gli1 was observed in normal liver tissue. KAAD-cyclopamine (KAAD-cyc), a specific inhibitor of the Hh pathway, at the concentrations of 1 and 4 μmol/L inhibited the invasion and migration of Bel-7402 cells and decreased the expression of Gli1 in nucleus and MMP-9, p-ERK1/2 proteins in Bel-7402 cells. On the other hand, Shh, a ligand of the Hh pathway, at the concentration of 0.5 μg/mL produced opposite effects. The MAPK pathway inhibitors U0126 and PD98059 at the concentrations of 5 and 10 μmol/L inhibited invasion and metastasis of Bel-7402 cells induced by Shh, and decreased the expression of p-ERK1/2 and MMP-9. However, U0126 and PD98059 had no effect on the expression of Gli1. Conclusion: Hh signaling pathway mediates invasion and metastasis of human HCC by up-regulating the protein expression of MMP-9 via ERK pathway.

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“…WNT, Notch, FGF, Hedgehog, and BMP signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis (1)(2)(3)(4)(5)(6)(7)(8). Canonical WNT signals are transduced through Frizzled receptors and LRP5/6 co-receptors to activate transcription of target genes, such as FGF18, FGF20, DKK1 and DKK4, based on the transcriptional complex consisting of TCF/LEF, ß-catenin, BCL9/BCL9L, and PYGO1/ PYGO2 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Comparative integromics on BMP/GDF family

Katoh¹,

Katoh²

2006

Int J Mol Med

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Abstract. WNT, Notch, FGF, Hedgehog and BMP signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis. BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMP10, BMP15, AMH, GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, GDF8, GDF9, GDF10, GDF11, and GDF15 are BMP/GDF family genes within the human genome; however, transcriptional regulation of BMP/GDF family members by the canonical WNT signaling pathway remains unclear. We searched for the TCF/LEF-binding site within the promoter region of BMP/GDF family genes by using bioinformatics and human intelligence. Because four TCF/LEF-binding sites were identified within human GDF10 promoter, comparative genomics analyses on GDF10 orthologs were further performed. Chimpanzee GDF10 gene, encoding a 477-amino-acid protein, was identified within NW_112875.1 genome sequence. AY412135.1 was not the correct coding sequence for chimpanzee GDF10. Chimpanzee GDF10 showed 99.2%, 83.2% and 47.4% total amino-acid identity with human GDF10, mouse Gdf10 and human BMP3, respectively. RASGEF1A-GDF10-PRKG1 locus at human chromosome 10q11 and BMP3-PRKG2-RASGEF1B locus at human chromosome 4q21 were paralogous regions with insertions/deletions and recombination. Human GDF10 mRNA was expressed in fetal cochlea, fetal lung, testis, retina, pineal gland, other neural tissues, head and neck tumors, while mouse Gdf10 mRNA was expressed in fetal liver, inner ear, cerebellum, other neural tissues, prostate and blood vessels. Four TCF/LEF-binding sites in human GDF10 promoter were conserved in chimpanzee GDF10 promoter, but not in the mouse Gdf10 promoter; however, another TCF/LEF-binding site occurred in mouse Gdf10 promoter. Four bHLH-binding sites in human GDF10 promoter were conserved in chimpanzee GDF10 promoter, but only one in mouse Gdf10 promoter. Primate GDF10 promoters were divergent from mouse Gdf10 promoter. Because GDF10 was characterized as a potential target of canonical WNT signaling pathway in neural tissues, GDF10 is one of the targets of systems medicine, especially in the field of regenerative medicine.

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Hedgehog signaling pathway and gastric cancer

Cited by 151 publications

References 52 publications

Hedgehog signaling pathway and gastrointestinal stem cell signaling network (Review)

Hedgehog signaling pathway and gastrointestinal stem cell signaling network (Review)

Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

Comparative integromics on BMP/GDF family

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