Up-regulation of DLK1 as an imprinted gene could contribute to human hepatocellular carcinoma

Huang, Jian; Zhang, Xin; Zhang, Min; Zhu, Jingde; Zhang, Yunli; Lin, Yun; Wang, Kesheng; Qi, Xiaofei; Zhang, Qin; Liu, Guang‐Zhen; Yu, Jian; Cui, Ying; Yang, Pengyuan; Wang, Zhiqin; Han, Ze‐Guang

doi:10.1093/carcin/bgl215

Cited by 94 publications

(92 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tak1ΔHEP mice spontaneously develop hepatocellular carcinoma associated with the reactivation of oncofetal genes, a common feature in human hepatocellular carcinoma and in murine liver cancer induced by treatment with DEN (17)(18)(19)(20)(21). Oncofetal liver genes expressed in the tumors of Tak1ΔHEP mice included α-fetoprotein, H19, insulin-like growth factor 2, delta-like 1 homolog, and reduced expression of 3.…”

Section: Tak1 Deficiency Increases Susceptibility To Tnf-α-mediated Hmentioning

confidence: 99%

“…1G). To further investigate the malignant potential of tumors in Tak1ΔHEP mice, the expression of fetal stage-specific liver genes, such as H19, insulin-like growth factor 2, delta-like 1 homolog, and reduced in expression 3 (encoded by H19, Igf2, Dlk1, and Rex3, respectively) were measured in tumors and nontumor liver from 9 month-old Tak1ΔHEP mice (17)(18)(19)(20)(21). High expression of fetal liver genes was seen exclusively in tumors and not in nontumor liver of Tak1ΔHEP mice or WT liver (Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis

Inokuchi¹,

Aoyama²,

Miura³

et al. 2009

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

249

274

View full text Add to dashboard Cite

TGF-β–activated kinase 1 (TAK1) is a MAP3K family member that activates NF-κB and JNK via Toll-like receptors and the receptors for IL-1, TNF-α, and TGF-β. Because the TAK1 downstream molecules NF-κB and JNK have opposite effects on cell death and carcinogenesis, the role of TAK1 in the liver is unpredictable. To address this issue, we generated hepatocyte-specific Tak1 -deficient ( Tak1ΔHEP ) mice. The Tak1ΔHEP mice displayed spontaneous hepatocyte death, compensatory proliferation, inflammatory cell infiltration, and perisinusoidal fibrosis at age 1 month. Older Tak1ΔHEP mice developed multiple cancer nodules characterized by increased expression of fetal liver genes including α-fetoprotein. Cultures of primary hepatocytes deficient in Tak1 exhibited spontaneous cell death that was further increased in response to TNF-α. TNF-α increased caspase-3 activity but activated neither NF-κB nor JNK in Tak1 -deficient hepatocytes. Genetic abrogation of TNF receptor type I (TNFRI) in Tak1ΔHEP mice reduced liver damage, inflammation, and fibrosis compared with unmodified Tak1ΔHEP mice. In conclusion, hepatocyte-specific deletion of TAK1 in mice resulted in spontaneous hepatocyte death, inflammation, fibrosis, and carcinogenesis that was partially mediated by TNFR signaling, indicating that TAK1 is an essential component for cellular homeostasis in the liver.

show abstract

Section: Tak1 Deficiency Increases Susceptibility To Tnf-α-mediated Hmentioning

confidence: 99%

mentioning

confidence: 99%

Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis

Inokuchi¹,

Aoyama²,

Miura³

et al. 2009

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

249

274

View full text Add to dashboard Cite

show abstract

“…Up-regulation of DLK was found in 73.2% of HCC specimens due to genomic methylation [84]. DLK1 (+) cells were found in all 17 HCC cell lines and exhibited stronger ability of in vitro clonogenicity and in vivo tumorigenicity in mice.…”

Section: Dlk1 (Delta-like 1 Homolog)mentioning

confidence: 99%

Surface markers of hepatocellular cancer stem cells and their clinical potential

Feng¹,

Wang²,

Hu³

et al. 2014

neo

View full text Add to dashboard Cite

Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into immune-comprised mice. Accumulating evidences have shown that CSCs or tumor-initiating cells are key drivers of tumor formation and progression in both solid tumors and haematological malignancies. Identification of the CSCs or tumor-initiating cells is a fundamental and important problem in cancer research. There is still a lack of consensus regarding the existence of a "global" marker for CSCs in different human cancers, but isolated CSCs have shown both the tumor-propagating ability in immune-compromised mice and the capacity to fully recapitulate the original heterogeneity of cell types. Several cell surface markers, including CD133, CD44 and CD90, were often used to identify and enrich CSCs. Although not all types of cancer follow the CSC theory, it provides an attractive cellular mechanism to account for the therapeutic resistance and recurrence of the disease. Here we provide a brief review regarding the markers for identification of CSCs in hepatocellular cancer, allowing us to deep understand of the cellular organization of HCC and to develop therapies that target specific CSCs.

show abstract

“…Identifying the genes that are differentially expressed in tumor from paratumor tissue is currently a topic of much interest. In recent years, with various transcriptome approaches, numerous upregulated oncogenes or downregulated tumor suppressor genes in HCC have been reported, such as IGF2, FAT10, SCARA5, DLK1 and p53 (5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

C9orf100, a new member of the Dbl-family guanine nucleotide exchange factors, promotes cell proliferation and migration in hepatocellular carcinoma

Wang

et al. 2012

Mol Med Report

View full text Add to dashboard Cite

Abstract. Dbl-family guanine nucleotide exchange factors (GEFs) are important activators of Rho GTPases, which are significantly associated with tumorigenesis and metastasis. The catalytic ability of the Dbl-family GEFs to activate Rho GTPases depends on their Dbl-homology domain followed by a pleckstrin-homology domain. In the present study, we showed that C9orf100, a new member of the Dbl-family GEFs with a minimal catalytic unit, may contribute to hepatocellular carcinoma (HCC). Quantitative real-time PCR results demonstrated that C9orf100 was highly and widely upregulated in 42/44 (95.5%, >2-fold) HCC specimens compared with adjacent non-cancerous livers, and this upregulation was correlated with intrahepatic metastasis and α-fetoprotein levels of HCC. Furthermore, the ectopic expression of C9orf100 promoted cell proliferation and colony formation in Huh-7 and YY-8103 cells, whereas silencing of C9orf100 resulted in the suppression of cell growth in MHCC-97H and PLC/PRF/5 cells. Flow cytometry confirmed this effect on MHCC-97H cell growth and indicated that C9orf100 may function in the G 2 /M phase. In addition, we showed that C9orf100 is involved in the positive regulation of HCC cell migration by a transwell chamber analysis. Our findings suggest that C9orf100 plays a potential oncogenic role in the development and metastasis of HCC. IntroductionHepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide, particularly in Asia and Africa. The main predisposing factors for its development include chronic infection with the hepatitis B and C virus, alcohol abuse and aflatoxin intake (1,2). Cirrhosis induced by a virus or alcohol poses the highest risk, as 80% of HCCs develop in cirrhotic livers (3). The primary treatments of HCC are surgical resection, liver transplantation, percutaneous ablation and conventional chemotherapy; however, prognosis of advanced HCC remains poor (4). Tumor recurrence and metastasis in HCC treatment are still the main problems. As with many other tumors, the development and progression of HCC is a complex multistep process and the molecular mechanisms involved in this process have yet to be fully clarified. Ongoing investigations to identify new and effective molecular targets controlling HCC progression are crucial for improving prognosis and treatment strategies.Activation of oncogenes and inactivation of tumor suppressor genes are frequently associated with carcinogenesis and progression. Identifying the genes that are differentially expressed in tumor from paratumor tissue is currently a topic of much interest. In recent years, with various transcriptome approaches, numerous upregulated oncogenes or downregulated tumor suppressor genes in HCC have been reported, such as IGF2, FAT10, SCARA5, DLK1 and p53 (5-9).The Rho family of small GTPases are key regulators of a variety of cellular events: cell cycle progression, cytoskeletal reorganization, membrane trafficking, cell migration and invasion (10,11). Previous studies have suggested that aberrant ...

show abstract

Up-regulation of DLK1 as an imprinted gene could contribute to human hepatocellular carcinoma

Cited by 94 publications

References 28 publications

Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis

Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis

Surface markers of hepatocellular cancer stem cells and their clinical potential

C9orf100, a new member of the Dbl-family guanine nucleotide exchange factors, promotes cell proliferation and migration in hepatocellular carcinoma

Contact Info

Product

Resources

About