EMT imparts cancer stemness and plasticity: new perspectives and therapeutic potential

Roy, Sayoni; Sunkara, Raghava R.; Parmar, Manan Y; Shaikh, Saima; Waghmare, Sanjeev K.

doi:10.2741/4893

Cited by 43 publications

(33 citation statements)

References 55 publications

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“…These results corroborate the findings of previous work in neoplastic transformation of non-cancer epithelial cells induced by Cd, which showed chronic Cd exposure induced epithelial cells into a more invasive and migratory phenotype by inducing EMT (Vanlaeys et al, 2020). EMT program has been shown to be crucial in tumor initiation, metastasis, cancer stemness and resistance to chemotherapy and radiation, and been associated with inferior cancer survival rate as well (Cheung et al, 2011;Loh et al, 2019;Roy et al, 2021). Combined with our earlier observations in chronic Cd-treated nasopharyngeal carcinoma cell model (Peng et al, 2019), these findings strongly suggest the carcinogenic and tumorpromoting effect of chronic Cd exposure in various human cancers.…”

Section: Discussionsupporting

confidence: 91%

Environmental Cadmium Exposure Promotes the Development, Progression and Chemoradioresistance of Esophageal Squamous Cell Carcinoma

Chen

Zhou²,

Lin³

et al. 2022

Front. Cell Dev. Biol.

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Cadmium (Cd) exposure has been implicated in the etiology of esophageal squamous cell carcinoma (ESCC), albeit with inconsistent results from epidemiologic studies and without causal evidence. In this study, we explore the relationship of Cd exposure and the development, progression and therapeutic resistance of ESCC. A total of 150 ESCC patients and 177 matched controls from a coastal region with a high incidence of ESCC in China were included in the study. It was found that the median blood Cd level (BCL) was significantly higher in ESCC patients than that in the controls. Odds ratios for ESCC risk were 3.12 (95% CI 1.54-6.30) and 3.71 (95% CI 1.84-7.48) in the third and fourth quartiles of Cd distribution, respectively. Notably, BCL above 4.71 μg/L was strongly associated with shorter progression-free survival time compared to that below 1.60 μg/L (p < 0.001). The chronic Cd-treated ESCC cells (CCT-ESCC) CCT-EC109 and CCT-EC9706 exhibited increased cell proliferation and tumorigenesis, enhanced migration and invasion, and upregulated EMT biomarkers following 12 weeks of exposure to 5 μM cadmium chloride. Furthermore, Cd treatment attenuated the efficacy of 5-fluorouracil, cisplatin and irradiation treatment in CCT-ESCC cells both in vitro and in vivo. Moreover, we revealed that Cd stimulated the cancer cell stemness and Wnt/β-catenin signaling pathway in the CCT-ESCC cells. Additionally, 5-aza-2-deoxy-cytidine treatment resulted in suppression of the Wnt/β-catenin signaling pathway and rescue of the Cd-induced cell radioresistance. These results offer new insights into the role of environmental Cd exposure in the development, progression and chemoradioresistance of ESCC.

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Section: Discussionsupporting

confidence: 91%

Environmental Cadmium Exposure Promotes the Development, Progression and Chemoradioresistance of Esophageal Squamous Cell Carcinoma

Chen

Zhou²,

Lin³

et al. 2022

Front. Cell Dev. Biol.

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“…EMT has been associated with cancer stemness, characterized by an increase in the number of cancer stem cells (CSCs) (13)(14)(15)(16). CSCs are subclone cells in the tumor tissue that obtain stem cell traits (17,18).…”

Section: Introductionmentioning

confidence: 99%

Communication Between Epithelial–Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression

Zheng

Dai²,

Feng

et al. 2021

Front. Oncol.

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The epithelial–mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is considered responsible for metastasis, relapse, and chemoresistance. Molecular links between the EMT and cancer stem cells (CSCs) have indicated that EMT processes play important roles in the expression of CSC-like properties. It is generally thought that EMT-related transcription factors (EMT-TFs) need to be downregulated to confer an epithelial phenotype to mesenchymal cells and increase cell proliferation, thereby promoting metastasis formation. However, the genetic and epigenetic mechanisms that regulate EMT and CSC activation are contradictory. Emerging evidence suggests that EMT need not be a binary model and instead a hybrid epithelial/mesenchymal state. This dynamic process correlates with epithelial–mesenchymal plasticity, which indicates a contradictory role of EMT during cancer progression. Recent studies have linked the epithelial–mesenchymal plasticity and stem cell-like traits, providing new insights into the conflicting relationship between EMT and CSCs. In this review, we examine the current knowledge about the interplay between epithelial–mesenchymal plasticity and CSCs in cancer biology and evaluate the controversies and future perspectives. Understanding the biology of epithelial–mesenchymal plasticity and CSCs and their implications in therapeutic treatment may provide new opportunities for targeted intervention.

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“…Furthermore, EMT-TFs, belonging to SNAIL, TWIST, and ZEB families, are responsible for the promotion of cancer stemness in various types of cancer, including nasopharyngeal carcinoma, breast cancer, colon cancer, etc. [ 124 , 125 , 126 , 127 ]. Additionally, the Wnt signaling pathway, Notch/Jagged pathway, and hedgehog signal pathway play important roles both in EMT and cancer stem cells [ 128 , 129 , 130 ].…”

Section: Conclusion and Perspectivementioning

confidence: 99%

MicroRNAs in Epithelial–Mesenchymal Transition Process of Cancer: Potential Targets for Chemotherapy

Peng

Fan

Sui

et al. 2021

IJMS

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In the last decades, a kind of small non-coding RNA molecules, called as microRNAs, has been applied as negative regulators in various types of cancer treatment through down-regulation of their targets. More recent studies exert that microRNAs play a critical role in the EMT process of cancer, promoting or inhibiting EMT progression. Interestingly, accumulating evidence suggests that pure compounds from natural plants could modulate deregulated microRNAs to inhibit EMT, resulting in the inhibition of cancer development. This small essay is on the purpose of demonstrating the significance and function of microRNAs in the EMT process as oncogenes and tumor suppressor genes according to studies mainly conducted in the last four years, providing evidence of efficient target therapy. The review also summarizes the drug candidates with the ability to restrain EMT in cancer through microRNA regulation.

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EMT imparts cancer stemness and plasticity: new perspectives and therapeutic potential

Cited by 43 publications

References 55 publications

Environmental Cadmium Exposure Promotes the Development, Progression and Chemoradioresistance of Esophageal Squamous Cell Carcinoma

Environmental Cadmium Exposure Promotes the Development, Progression and Chemoradioresistance of Esophageal Squamous Cell Carcinoma

Communication Between Epithelial–Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression

MicroRNAs in Epithelial–Mesenchymal Transition Process of Cancer: Potential Targets for Chemotherapy

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