Loss of Claudin-1 Expression Correlates with Malignancy of Hepatocellular Carcinoma

Higashi, Yukihiro; Suzuki, Shohachi; Sakaguchi, Takanori; Nakamura, Takamitsu; Baba, Satoshi; Reinecker, Hans Christian; Nakamura, Satoshi; Konno, Hiroyuki

doi:10.1016/j.jss.2006.08.038

Cited by 89 publications

(62 citation statements)

References 32 publications

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“…Attenuated expression of claudin-1 closely correlates with the dedifferentiation and portal invasion of hepatocellular carcinoma [35]. Defect in claudin-1 expression increases paracellular permeability in polarized hepatic cell lines, supporting the hypothesis that paracellular bile leakage through deficient TJs is involved in liver pathology observed in NISCH syndrome [28].…”

Section: Discussionmentioning

confidence: 59%

“…During cancer development, the expression of several TJ components usually decreases [27,28,35], however, elevated expression of TJ components have been detected in certain tumors [9,[36][37][38]. In contrast to hepatocellular carcinoma (HCC) [7,39], overexpression of claudin-4 has been observed in cholangiocarcinoma [29], in colon cancer [40], in pancreatic ductal carcinoma [41] and in several other malignancies [37,42,43].…”

Section: Introductionmentioning

confidence: 99%

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Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

Erdélyi-Belle

Török

Apáti

et al. 2015

Pathol. Oncol. Res.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

Erdélyi-Belle

Török

Apáti

et al. 2015

Pathol. Oncol. Res.

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“…Claudin-3 and claudin-4 have also been shown to be overexpressed in breast, gastric, ovarian and pancreatic cancers (10)(11)(12). In contrast, Higashi et al (1) reported reduced levels of claudin-1 in malignant hepatocellular carcinoma, and another researcher demonstrated that claudin down-regulation is associated with higher invasiveness (13). The results described above confirm not only that claudins are dysregulated in many types of cancer, but also that the nature of this dysregulation is highly specific according to cancer type.…”

Section: Modulation Of Egr-1 Expression As Well As Metastasis-involvementioning

confidence: 99%

“…Patients whose liver cancer has metastasized have poor prognoses and therefore novel prevention strategies are urgently required in order to save lives (1). In this study, we present a new paradigm for the prevention of liver cancer metastasis by using histone deacetylase (HDAC) inhibitors to induce early growth response gene-1 (Egr-1), a Cys2-His2-typed zinc-finger transcription factor, and the restoration of tight junctions (TJs) in liver cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells

Kim

Choi

Choi³

et al. 2009

BMB Reports

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“…Similarly, in hepatocellular carcinoma, claudin-1 expression was reduced in poorly differentiated hepatocellular carcinomas. 63 The decrease in claudin-1 expression mediated by Src may be associated with dedifferentiation in colon cancer tumorigenesis. However, dedifferentiation cannot be primarily attributed to the claudin-1 decrease; claudin-1 overexpession in the colon cancer cell line SW480 actually resulted in dedifferentiation.…”

Section: Discussionmentioning

confidence: 99%

Src kinase induces tumor formation in the c‐SRC C57BL/6 mouse

Kline

Jackson

Engelman

et al. 2008

Intl Journal of Cancer

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Src kinase has been linked as a causative agent in the progression of a number of cancers including colon, breast, lung and melanoma. Src protein and activity levels are increased in colorectal cancer and liver metastases arising secondary to colon cancer. However, although Src protein is increased in colon cancer as early as the adenomatous polyp stage, a role for Src in carcinogenesis has not been established. We developed the c-SRC transgenic mouse in the C57BL/6 strain to address the issue of carcinogenesis in cells with high levels of Src expression. The transgene was constructed with the human c-SRC gene downstream of the mouse metallothionein promoter to create zinc inducible gene expression. In these C57BL/6 mice, Src protein was increased in a number of tissues both with and without zinc induction. No additional carcinogenic agent was administered. After 20 months, mice were assessed for tumor development in the liver and GI tract, as well as other organs. Of the mice with the transgene, 15% developed tumors in the liver while no tumors were detected in wild type C57BL/6 mice. A further study was conducted by crossing c-SRC C57BL/6 mice with p21 nullizygous mice to determine the effect of oncogene expression combined with inactivation of the tumor suppressor gene, p21. Addition of the c-SRC transgene to the p212/2 background increased tumor formation almost 3-fold, while it increased metastasis 6-fold. The data from our study show, for the first time, that Src kinase may play a role in carcinogenesis. ' 2008 Wiley-Liss, Inc.Key words: Src; transgenic mice; p21; carcinogenesis; metastasis Src is a nonreceptor tyrosine kinase that induces signal transduction in multiple pathways regulating cellular behavior. 1-3 Previous studies have shown that Src kinase activity is elevated in a variety of human cancers, 4-8 and has been linked with the progression and metastasis of cancer in humans. However, the exact role of Src in these processes remains elusive. 9-11 Src has been the focus of a number of studies using cultured cells, human tissues, and nude mouse experiments. [11][12][13][14][15][16] Src activity was shown to be important for tumor formation and metastasis in mouse models of prostate, ovarian and colon tumors, often through VEGF, Akt and Erk pathways. [17][18][19][20] Fibroblasts transfected with activated Src show a transformed phenotype when used in soft agar assays and in nude mouse models of metastasis. 21 Src has been shown to increase migration and invasion of human colon cancer cells in vitro. [22][23][24][25] The increase in invasion may be a result of a variety of events including altered activity of adhesion proteins, integrins and cadherins 26,27 and altered secretion of proteinases into the extracellular matrix. 28 However, while Src levels are increased during the progression of colorectal cancer as early as adenomatous polyps, there is little proof that Src initiates tumor development. To study the tumorigenicity of the Src protein, we developed a c-SRC C57BL/6 mouse model.Mouse model...

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Loss of Claudin-1 Expression Correlates with Malignancy of Hepatocellular Carcinoma

Abstract: Attenuated expression of CL-1 closely correlates with the dedifferentiation and portal invasion of HCC. Down-regulated CL-1 expression may serve as a potential marker for a poor prognosis in HCC.

Cited by 89 publications

References 32 publications

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells

Src kinase induces tumor formation in the c‐SRC C57BL/6 mouse

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