Epithelial-Mesenchymal Transition: A Hallmark in Metastasis Formation Linking Circulating Tumor Cells and Cancer Stem Cells

Książkiewicz, Magdalena; Markiewicz, Aleksandra; Żaczek, Anna

doi:10.1159/000337106

Cited by 171 publications

(143 citation statements)

References 331 publications

(232 reference statements)

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“…EMT, a process whereby epithelial cells reduce their intercellular adhesions and gain mesenchymal properties, is a critical event in the process of cancer invasion and metastasis (27,28). During liver cancer metastasis, epithelial cell-like HCC cells gain a mesenchymal phenotype characterized by an increase in cell migration and the ability to degrade the extracellular matrix (ECM) (27,29). These observations suggest that EMT may play an important role in HCC metastasis.…”

Section: Elk3 Promotes the Migration And Invasion Of Liver Cancer Stementioning

confidence: 99%

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

et al. 2016

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Abstract. Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the third most common cause of cancer-related mortality. HCC develops via a multistep process associated with genetic aberrations that facilitate HCC invasion and migration and promote metastasis. A growing body of evidence indicates that cancer stem cells (CSCs) are responsible for tumorigenesis, cancer cell invasion and metastasis. Despite the extremely small proportion of cancer cells represented by this subpopulation of HCC cells, CSCs play a key role in cancer metastasis and poor prognosis. ELK3 (Net/SAP-2/Erp) is a transcription factor that is activated by the Ras/extracellular signal-regulated kinase (ERK) signaling pathway. It plays several important roles in various physiological processes, including cell migration, invasion, wound healing, angiogenesis and tumorigenesis. In the present study, we investigated the role of ELK3 in cancer cell invasion and metastasis in CD133 + /CD44 + liver cancer stem cells (LCSCs). We isolated LCSCs expressing CD133 and CD44 from Huh7 HCC cells and evaluated their metastatic potential using invasion and migration assays. We found that CD133 + /CD44 + cells had increased metastatic potential compared with non-CD133 + /CD44 + cells. We also demonstrated that ELK3 expression was upregulated in CD133 + /CD44 + cells and that this aberration enhanced cell migration and invasion. In addition, we identified the molecular mechanism by which ELK3 promotes cancer cell migration and invasion. We found that silencing of ELK3 expression in CD133 + /CD44 + LCSCs attenuated their metastatic potential by modulating the expression of heat shock-induced factor-1α (HIF-1α). Collectively, the results of the present study demonstrated that ELK3 overexpression promoted metastasis in CD133 + /CD44 + cells by regulating HIF-1α expression and that silencing of ELK3 expression attenuated the metastatic potential of CD133 + /CD44 + LCSCs. In conclusion, modulation of ELK3 expression may represent a novel therapeutic strategy for preventing HCC metastasis and invasion.

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Section: Elk3 Promotes the Migration And Invasion Of Liver Cancer Stementioning

confidence: 99%

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

et al. 2016

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“…During this process, the phenotype of cancer cells undergoes alterations in cellular morphology, with increased expression of mesenchymal markers such as vimentin and decreased expression of epithelial markers such as E-cadherin (15). These changes are associated with decreased cell adhesion capacity, leading to enhanced invasion and metastasis (15,16). Consequently, EMT inhibition represents a significant target for the development of prostate cancer treatments.…”

Section: Discussionmentioning

confidence: 99%

Curcumin mediates reversion of HGF-induced epithelial-mesenchymal transition via inhibition of c-Met expression in DU145 cells

Lin

Liu

et al. 2015

Oncology Letters

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Abstract. The hepatocyte growth factor (HGF)/c-Met signaling pathway results in cancer cell scattering and invasion, and has been reported to participate in several types of cancer, including prostate and colorectal cancer. The downstream phosphorylation cascade of HGF, particularly the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT signaling pathway, regulates epithelial-mesenchymal transition (EMT). However, the mechanism by which these signaling pathways govern EMT, and whether certain kinases are able to respond to specific EMT effectors, remains to be elucidated. In the present study, an increase in the levels of vimentin, rather than co-regulation of certain EMT marker proteins, was observed in response to HGF-induced EMT in DU145 prostate cancer cells. In addition, it was observed that curcumin abrogated HGF-induced DU145 cell scattering and invasion. Furthermore, curcumin was able to effectively inhibit the HGF-induced increase in the levels of vimentin by downregulating the expression of phosphorylated c-Met, extracellular signal-regulated kinase and Snail. In conclusion, the results of the present study demonstrated that curcumin was able to reverse HGF-induced EMT, possibly by inhibiting c-Met expression in DU145 prostate cancer cells.

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“…The occurrence of EMT during tumor progression allows tumor cells to acquire the capacity to infiltrate surrounding tissue and metastasize to distant sites ultimately (Ksiazkiewicz et al, 2012;Zhu et al, 2013). Several transcription factors, including theSnail/Slug family, Twist, ZEB1, SIP1/ZEB2 and Twist respond to microenvironmental stimuli and function as molecular switches for the EMT program .…”

Section: Discussionmentioning

confidence: 99%

Silencing of COX-2 by RNAi Modulates Epithelial-Mesenchymal Transition in Breast Cancer Cells Partially Dependent on the PGE₂Cascade

Cao

Xiao²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Epithelial-Mesenchymal Transition: A Hallmark in Metastasis Formation Linking Circulating Tumor Cells and Cancer Stem Cells

Cited by 171 publications

References 331 publications

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

Curcumin mediates reversion of HGF-induced epithelial-mesenchymal transition via inhibition of c-Met expression in DU145 cells

Silencing of COX-2 by RNAi Modulates Epithelial-Mesenchymal Transition in Breast Cancer Cells Partially Dependent on the PGE₂Cascade

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Epithelial-Mesenchymal Transition: A Hallmark in Metastasis Formation Linking Circulating Tumor Cells and Cancer Stem Cells

Cited by 171 publications

References 331 publications

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

Curcumin mediates reversion of HGF-induced epithelial-mesenchymal transition via inhibition of c-Met expression in DU145 cells

Silencing of COX-2 by RNAi Modulates Epithelial-Mesenchymal Transition in Breast Cancer Cells Partially Dependent on the PGE2Cascade

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Silencing of COX-2 by RNAi Modulates Epithelial-Mesenchymal Transition in Breast Cancer Cells Partially Dependent on the PGE₂Cascade