Epithelial–Mesenchymal Transition in Hepatocellular Carcinoma

Zijl, Franziska van; Zulehner, Gudrun; Petz, Michaela; Schneller, Doris; Kornauth, Christoph; Hau, Mara; Machat, Georg; Grubinger, Markus; Huber, Heidemarie; Mikulits, Wolfgang

doi:10.2217/fon.09.91

Cited by 281 publications

(231 citation statements)

References 64 publications

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“…For different types of tumors it has been demonstrated that an EMT-switch is associated with a worse prognosis as seen in esophageal squamous cell carcinoom [81] , gastric cancer cells [82] bladder cancer [83] non-small cell lung cancer [84] and pancreas ductal adenomacarcinoma [85] . For HCC, this correlation has also been found with an independent effect of Twist and Snail in promoting metastasis of hepatocellular carcinoma [86][87][88][89] .…”

Section: Hepatocarcinogenesis and Tumormicroenviromentmentioning

confidence: 81%

See 1 more Smart Citation

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Severi¹,

Malenstein²,

Verslype³

et al. 2010

Acta Pharmacol Sin

157

125

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Section: Hepatocarcinogenesis and Tumormicroenviromentmentioning

confidence: 81%

“…Important molecular pathway involved in EMT are Wnt/betacatenin signaling [95,96] and through growth factor signalling like PDGF [97] .…”

Section: Hepatocarcinogenesis and Tumormicroenviromentmentioning

confidence: 99%

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Severi¹,

Malenstein²,

Verslype³

et al. 2010

Acta Pharmacol Sin

157

125

View full text Add to dashboard Cite

“…EMT allows benign tumors to progress into metastatic cancers that can invade other tissues. 39 The evaluation and comparison of miRNAs in human cancers and EMT can provide insights into the type of miRNAs that regulate EMT to drive the transformation of tumor. In Table 2, we have summarized the EMT-associated miRNAs that have been identified and their target genes in various cancer types.…”

Section: Mirnas In Emt Transition and Cancer Metastasismentioning

confidence: 99%

MicroRNAs involved in regulating epithelial–mesenchymal transition and cancer stem cells as molecular targets for cancer therapeutics

Xia

Hui

2012

Cancer Gene Ther

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One of the major challenges in cancer gene therapy is the identification of functionally relevant tumor-specific genes as the therapeutic targets. MicroRNAs (miRNAs) are a class of small, 22-25 nucleotides, endogenously expressed noncoding RNA. miRNAs are important genetic regulators: one miRNA can possibly target multiple genes and they can function as tumor promoters (oncogenic miRNAs, oncomirs) or tumor suppressors (anti-oncomirs). Therefore, the identification of misregulated miRNAs in cellular signaling pathways related to oncogenesis can have profound implications for cancer therapy. The epithelial-mesenchymal transition (EMT) converts epithelial cells into mesenchymal cells, a normal embryological process that frequently get activated during cancer invasion and metastasis. Recent evidence also supports the presence of a small subset of self-renewing, stem-like cells within the tumor mass that possess the capacity to seed new tumors and they have been termed 'cancer stem cells (CSC)'. Conceivably, these CSCs could provide a resource for cells that cause therapy resistance. Although the cell origin of CSCs remains to be fully elucidated, a growing body of evidence has demonstrated that the biology of EMT and CSCs is tightly linked with the sequences and compositions of miRNA molecules. Therefore, targeting miRNAs involved in EMT and CSCs regulation can provide novel miRNA-based therapeutic strategies in oncology.

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“…23 In addition, the partial recurrence of embryonic programs, such as TGF-b and Wnt/b-catenin signaling, is present in HCC. 24 Nonetheless, the detailed signaling mechanisms of EMT and HCC metastasis is not well defined, and the growing body of respective studies has yet to reach consensus.…”

mentioning

confidence: 99%

Notch1‐Snail1‐E‐cadherin pathway in metastatic hepatocellular carcinoma

Wang

Zhang

Lui

et al. 2011

Intl Journal of Cancer

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Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the reestablishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis.Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and is ranked second amongst all cancer deaths in Hong Kong. HCC is correlated with an increased likelihood of vascular invasion, metastasis and recurrence (even after surgical resection), leading to poor prognosis. 1 Metastasis, both intrahepatic and extrahepatic, is of particular concern and occurs in more than half of HCC cases. 2 The incidence of high grade HCC that metastasize to distant sites is high. 2 However, the detailed mechanisms of metastasis are yet to be revealed.The process that converts adherent epithelial cells into migratory cells to invade the extracellular matrix is called the epithelial-mesenchymal transition (EMT). This process plays fundamental roles in tissue and organ formation during embryonic development and in wound healing and tissue repair during adult life. 3,4 However, the abnormal activation of EMT programs can be disadvantageous to cancer patients. 3 EMT can allow carcinoma cells to acquire mesenchymal cell gene expression profiles and properties, 5 leading to the transformation of the cells from being coherent and displaying apicobasal polarity to become nonpolarized cells that can move through the extracellular media. This transformation enables the spread of tumor cells to distant sites. 6,7 Although EMT is considered to be the first step in the metastatic progression of migratory cancer cells, EMT has not been confirmed to exist in vivo. 3...

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Epithelial–Mesenchymal Transition in Hepatocellular Carcinoma

Cited by 281 publications

References 64 publications

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

MicroRNAs involved in regulating epithelial–mesenchymal transition and cancer stem cells as molecular targets for cancer therapeutics

Notch1‐Snail1‐E‐cadherin pathway in metastatic hepatocellular carcinoma

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