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Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer

1
Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, 50937 Cologne, Germany
2
Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
3
Singleron Biotechnologies, Yaogu Avenue 11, Nanjing 210000, China
4
Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany
5
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, 4107 Leipzig, Germany
6
Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Cells 2020, 9(6), 1481; https://doi.org/10.3390/cells9061481
Received: 30 April 2020 / Revised: 7 June 2020 / Accepted: 10 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Cancer Stem Cells and Resistance to Therapy)
Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer. View Full-Text
Keywords: esophageal cancer; heterogeneity; cancer stem cell; plasticity; therapeutic resistance esophageal cancer; heterogeneity; cancer stem cell; plasticity; therapeutic resistance
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Zhou, C.; Fan, N.; Liu, F.; Fang, N.; Plum, P.S.; Thieme, R.; Gockel, I.; Gromnitza, S.; Hillmer, A.M.; Chon, S.-H.; Schlösser, H.A.; Bruns, C.J.; Zhao, Y. Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer. Cells 2020, 9, 1481.

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