Telomere length, TERT and shelterin complex proteins in hepatocellular carcinomas expressing “stemness”-related markers

Kim, Haeryoung; Yoo, Jeong Eun; Cho, Jai Young; Oh, Bong Kyeong; Yoon, Yoo Seok; Han, Ho Seong; Lee, Hye Seung; Jang, Ja June; Jeong, Sook Hyang; Kim, Jin Wook; Park, Young Nyun

doi:10.1016/j.jhep.2013.05.011

Cited by 59 publications

(58 citation statements)

References 24 publications

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“…Next, since chronic DDC feeding induces activation of LPC [123], I evaluated the amount of activated LPC and found less LPCs in DDC-fed K19-KOs, indicating that K19 plays an essential role in DDC-induced LPC proliferation during biliary regeneration. This is consistent with a recent study showing that K19 expression in HCC was associated with increased tumor size and bad prognosis [52, 54,191]. Furthermore, our finding might be relevant to the pathogenesis of biliary diseases such as PBC since K19 variants, K19 G17S, was identified in patients with advanced PBC [57].With regard to our findings, it is tempting to speculate that diminished regenerative ability in K19 deficient ductal cells may contribute to the development of ductopenia that is seen in advanced PBC.…”

Section: Decreased Ddc-induced Ductular Reaction and Lpc Proliferatiosupporting

confidence: 93%

940 Loss of Keratin 19 Predisposes to the Development of Cholestatic Liver Disease

Chen¹,

Güldiken²,

Omary³

et al. 2012

Journal of Hepatology

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Section: Decreased Ddc-induced Ductular Reaction and Lpc Proliferatiosupporting

confidence: 93%

940 Loss of Keratin 19 Predisposes to the Development of Cholestatic Liver Disease

Chen¹,

Güldiken²,

Omary³

et al. 2012

Journal of Hepatology

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“…Furthermore, overexpression of "stemness"-related proteins (including c-KIT, K19, and CD34) was shown to be associated with aggressive HCC and poor prognosis [135][136][137][138] . Recently, the stem-cell factor, a ligand of c-KIT, was shown to be an independent prognostic factor for HCC after resection [139] .…”

Section: Tissue Biomarkersmentioning

confidence: 99%

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

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Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.

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“…Various molecular profiling approaches have been used to identify potential therapeutic targets which are specifically activated in HCC [4][5][6][7][8]. Some studies have indicated the importance of evaluating ''stemness'' in HCC; it reflects the malignant nature of the tumor and closely correlates with a poor prognosis after surgery [9][10][11][12]. Recent evidence has also suggested that HCC may conform to the cancer stem cell (CSCs) hypothesis, which proposes that a subset of cells with stem cell features play a fundamental role in tumor maintenance and chemo/radiation resistance [13].…”

Section: Introductionmentioning

confidence: 99%

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

Nio

Yamashita

Okada

et al. 2015

Journal of Hepatology

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Background & Aims: Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM + liver cancer stem cells. Methods: Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of CHD4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. Results: CHD4 was abundantly expressed in EpCAM + hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of CHD4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM + liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model.Conclusions: CHD4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma. Ó

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Telomere length, TERT and shelterin complex proteins in hepatocellular carcinomas expressing “stemness”-related markers

Cited by 59 publications

References 24 publications

940 Loss of Keratin 19 Predisposes to the Development of Cholestatic Liver Disease

940 Loss of Keratin 19 Predisposes to the Development of Cholestatic Liver Disease

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

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