Activation of sonic hedgehog signaling pathway is an independent potential prognosis predictor in human hepatocellular carcinoma patients

Li, Qing; Che,; Yanhua,; Zhong, Yuan; Jun, Jun; Jia, Jia; Ren$^{, }$

doi:10.1007/s11670-012-0271-z

Cited by 39 publications

(27 citation statements)

References 43 publications

(77 reference statements)

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“…Moreover, GLI1-positive hepatocellular carcinoma specimens showed poorly differentiated phenotypes (Table 2), whereas all of GLI1-negative hepatocellular carcinoma specimens showed moderately differentiated phenotypes. These results are consistent in part with the implication of GLI1 expression as a poor prognosis marker (Che et al 2012). The positive rate for GLI1 immunoreactivity was significantly lower in female patients than the rate in male patients (P = 0.03, Table 2).…”

Section: Expression Profiles Of Mitf In Hepatocellular Carcinomasupporting

confidence: 80%

“…Importantly, MITF is co-expressed with GLI1, a poor prognosis marker for hepatic cancer (Che et al 2012). The clinical data also support that MITF expression is a poor prognosis marker for hepatocellular carcinoma (Table 1).…”

Section: Cytoplasmic Expression Of Mitf In Hepatocellular Carcinoma Amentioning

confidence: 58%

“…Because we used two separate tissue arrays containing the same series of cancer specimens, it is not necessarily possible to analyze the consecutive tissue sections. GLI1 expression was also analyzed as a poor prognosis marker of hepatocellular carcinoma (Che et al 2012). Fig.…”

Section: Expression Profiles Of Mitf In Hepatocellular Carcinomamentioning

confidence: 99%

“…In fact, we have shown that GLI1 immunoreactivity was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens) (see Tables 2 and 5). Furthermore, GLI1 has been shown as a poor prognosis marker for hepatic cancer (Che et al 2012). Importantly, MITF is co-expressed with GLI1 only in subsets of hepatocellular carcinoma and cholangiocarcinoma.…”

Section: Potential Role Of Hedgehog Signaling For Regulation Of Mitf mentioning

confidence: 99%

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Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma

Nooron

Ohba

Takeda

et al. 2017

Tohoku J. Exp. Med.

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Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is overexpressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

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Section: Expression Profiles Of Mitf In Hepatocellular Carcinomasupporting

confidence: 80%

Section: Cytoplasmic Expression Of Mitf In Hepatocellular Carcinoma Amentioning

confidence: 58%

Section: Expression Profiles Of Mitf In Hepatocellular Carcinomamentioning

confidence: 99%

Section: Potential Role Of Hedgehog Signaling For Regulation Of Mitf mentioning

confidence: 99%

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Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma

Nooron

Ohba

Takeda

et al. 2017

Tohoku J. Exp. Med.

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“…The sonic hedgehog (SHH) signaling pathway is a highly conserved system; it is involved in proliferation and control of the migration and invasion of HCC (3)(4)(5)(6). A number of SHH signaling pathway molecular inhibitors, such as cyclopamine, have demonstrated clinical efficacy against basal cell carcinoma, medulloblastoma and pancreatic cancer (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

BRD4 induces cell migration and invasion in HCC cells through MMP-2 and MMP-9 activation mediated by the Sonic hedgehog signaling pathway

Wang

Sui

et al. 2015

Oncology Letters

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Abstract. Hepatocellular carcinoma (HCC) is a highly aggressive form of carcinoma with poor prognosis, and HCC-associated mortality primarily occurs due to migration and invasion of HCC cells. The manipulation of epigenetic proteins, such as BRD4, has recently emerged as an alternative therapeutic strategy. The present study aimed to investigate the novel mechanism of BRD4 involvement in the migration and invasion of HCC cells. Reverse transcription-quantitative polymerase chain reaction was used to assess BRD4 mRNA expression levels in HCC cell lines. This analysis demonstrated that BRD4 was significantly overexpressed in HCC cell lines compared with a human immortalized normal liver cell line. A short hairpin RNA (shRNA) was then used to suppress BRD4 expression in HCC cells, and resulted in impaired HCC cell proliferation, migration and invasion. When the HepG2 HCC cell line was treated with recombinant human sonic hedgehog (SHH) peptide, the migration and invasion capabilities of HepG2 cells that were inhibited by BRD4 silencing were restored. BRD4 induced cell migration and invasion in HepG2 cells through the activation of matrix metalloproteinase (MMP)-2 and MMP-9, mediated by the SHH signaling pathway. Taken together, the results of the present study demonstrated the importance of BRD4 in HCC cell proliferation and metastasis. Thus, BRD4 is a potential novel target for the development of therapeutic approaches against HCC.

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Hedgehog signaling in the liver

Machado¹,

Diehl²

2015

Signaling Pathways in Liver Diseases

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Activation of sonic hedgehog signaling pathway is an independent potential prognosis predictor in human hepatocellular carcinoma patients

Cited by 39 publications

References 43 publications

Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma

Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma

BRD4 induces cell migration and invasion in HCC cells through MMP-2 and MMP-9 activation mediated by the Sonic hedgehog signaling pathway

Hedgehog signaling in the liver

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