The Epithelial-Mesenchymal Transition and Cancer Stem Cells: Functional and Mechanistic Links

Liu, Xiangqiang; Fan, Daiming

doi:10.2174/1381612821666141211115611

Cited by 126 publications

(100 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, integrin binding to collagen I can contribute to transcription factor activation including NFκB, Snail, and LEF. There are excellent reviews covering different aspects of EMT in CIC (Gonzalez and Medici, 2014; Chang et al, 2015; Liu and Fan, 2015; Liao and Yang, 2017) and, though much is known, due to the multiple levels of interactions, many open questions remain. We will only review some EMT-related processes describing an engagement of CD44.…”

Section: Linking Cd44/cd44v6 Activities To Cic Featuresmentioning

confidence: 99%

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

Wang

Zhao

Hackert

et al. 2018

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Metastasis is the leading cause of cancer death, tumor progression proceeding through emigration from the primary tumor, gaining access to the circulation, leaving the circulation, settling in distant organs and growing in the foreign environment. The capacity of a tumor to metastasize relies on a small subpopulation of cells in the primary tumor, so called cancer-initiating cells (CIC). CIC are characterized by sets of markers, mostly membrane anchored adhesion molecules, CD44v6 being the most frequently recovered marker. Knockdown and knockout models accompanied by loss of tumor progression despite unaltered primary tumor growth unraveled that these markers are indispensable for CIC. The unexpected contribution of marker molecules to CIC-related activities prompted research on underlying molecular mechanisms. This review outlines the contribution of CD44, particularly CD44v6 to CIC activities. A first focus is given to the impact of CD44/CD44v6 to inherent CIC features, including the crosstalk with the niche, apoptosis-resistance, and epithelial mesenchymal transition. Following the steps of the metastatic cascade, we report on supporting activities of CD44/CD44v6 in migration and invasion. These CD44/CD44v6 activities rely on the association with membrane-integrated and cytosolic signaling molecules and proteases and transcriptional regulation. They are not restricted to, but most pronounced in CIC and are tightly regulated by feedback loops. Finally, we discuss on the engagement of CD44/CD44v6 in exosome biogenesis, loading and delivery. exosomes being the main acteurs in the long-distance crosstalk of CIC with the host. In brief, by supporting the communication with the niche and promoting apoptosis resistance CD44/CD44v6 plays an important role in CIC maintenance. The multifaceted interplay between CD44/CD44v6, signal transducing molecules and proteases facilitates the metastasizing tumor cell journey through the body. By its engagement in exosome biogenesis CD44/CD44v6 contributes to disseminated tumor cell settlement and growth in distant organs. Thus, CD44/CD44v6 likely is the most central CIC biomarker.

show abstract

Section: Linking Cd44/cd44v6 Activities To Cic Featuresmentioning

confidence: 99%

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

Wang

Zhao

Hackert

et al. 2018

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…In addition, CSCs usually exhibit EMT properties. This mutual relationship between EMT and CSCs might be related to tumor progression [178]. The study of Goncalves and colleagues demonstrated that melatonin exhibited an inhibitory role in the viability and invasiveness of breast cancer mammospheres as well as in inhibiting the expression of OCT4, N-cadherin and vimentin proteins associated with EMT in breast CSCs [19].…”

Section: Discussionmentioning

confidence: 99%

The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

View full text Add to dashboard Cite

Aim: Cancer stem cells (CSCs) exhibited an excessive migratory and invasive potential. Melatonin may inhibit multiple crucial signals associated with tumor stem cell self-renewal, viability, invasiveness, tumor growth, and therapy resistance. Carbon ion irradiation may be a promising therapeutic modality in both non-stem-like and stem-like tumor cells in contrast to photon irradiation. A comprehensive understanding of the mechanisms and molecular pathways associated with invasive properties of CSCs is essential in developing novel treatment options for cancer therapy that target CSCs. Materials and methods:A systematic review of the existing literature was conducted using the following search terms: 'melatonin', 'X-ray irradiation', 'charged particle irradiation', 'carbon ion irradiation', 'cancer stem cells', 'tumor-initiating cells' and 'cancer stem-like cells'. The search used PubMed and spanned the period from January 2000 to December 2016. Conclusion:Cancer stem cells possess the capacity of self-renewal and pluripotency, generating all cells within a tumor, and are responsible for tumor growth, therapy resistance and metastasis. Melatonin attenuated AKT activation, EZH2 S21 phosphorylation, EZH2-STAT3 interactions and altered histone modifications to reduce tumor initiation and propagation of brain tumor stem cells (BTSC). Melatonin increases the efficacy of chemotherapeutic agents, targeting both the tumor bulk and BTSCs through the regulation of the expression and function of the ABCG2/BCRP transporter by inducing the methylation of its promoter. Melatonin treatment induced cell death with ultrastructural characteristics of autophagy. Breast cancer stem cells (BCSCs) are responsive to melatonin treatment by way of reducing the viability and the invasiveness of breast cancer mammospheres as well as regulating the expression of OCT4, N-cadherin and vimentin proteins associated with epithelial mesenchymal transition in BCSCs. Carbon irradiation is effective in brain tumor stem cell (BTSC) elimination with relative biologic effectiveness (RBE) in the range of 1.87-3.44. Carbon ion irradiation may be a promising therapeutic modality because it reduces migration and invasion processes in both head and neck squamous cell carcinoma and cancer stem cells in contrast to photon irradiation. Low LET X-ray irradiation may essentially eradicate the non-stem-like tumor cells, consequently the radioresistant cancer stem-like cell population is obviously enriched. In contrast, carbon ion irradiation may eradicate both non-stemlike and stem-like tumor cells at the same time. Carbon ion irradiation is a promising tool to eradicate putative colon cancer stem-like cells. Further investigation to elucidate the mechanisms and molecular pathways involved in cancer stem cells particularly associated with melatonin and carbon ion irradiation certainly is warranted.

show abstract

“…EMT is a highly conserved cell process involved in normal embryogenesis and tissue repair (Liu and Fan, 2015). Recently, numerous studies have shown that EMT plays a momentous role in tumor progression.…”

Section: Intracellular Markers In Renal Cscsmentioning

confidence: 99%

Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

Yuan

GuiXian

et al. 2016

Front. Pharmacol.

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rationale for therapies targeting this aggressive cell population. Precise identification of renal CSC populations and the complete cell hierarchy will accurately inform characterization of disease subtypes. This will ultimately contribute to more personalized and targeted therapies. Here, we summarize potential targeting strategies for renal cancer cells and renal CSCs, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTOR), interleukins, CSC marker inhibitors, bone morphogenetic protein-2, antibody drug conjugates, and nanomedicine. In conclusion, targeting therapies for RCC represent new directions for exploration and clinical investigation and they plant a seed of hope for advanced clinical care.

show abstract

The Epithelial-Mesenchymal Transition and Cancer Stem Cells: Functional and Mechanistic Links

Cited by 126 publications

References 0 publications

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

The impact of melatonin and carbon ion irradiation on cancer stem cells

Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

Contact Info

Product

Resources

About