Selma Zargari - Medical Genetics Research Center, Faculty Of Medicine, Mashhad University Of Medical Sciences,Mashhad, Iran
Dina Javid - Department Of Clinical Biochemistry, Mashhad University Of Medical Science, Mashhad, Iran
Meysam Moghbeli - Division Of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University Of Medical Sciences, Mashhad, Iran
Mohammad Mahdi Forghanifard - Department Of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

Esophageal squamous cell carcinoma (ESCC) is a standout amongst common malignancies around the world and is the sixth leading cause of cancer-related deaths. In spite of the fact that the diagnosis and treatment of EC have enhanced significantly, it has a poor prognosis for its metastasis, high recurrence rate, and treatment resistance. Cancer stem cells (CSCs) are an essential subpopulation of cells which are related to poor prognosis of patients with ESCC through renewal and repair. Several signaling pathways such as Notch, Wnt, Hedgehog and Hippo have been implicated in aggressive tumorbehavior brought about by CSCs. Intracellular molecules, for example, PYGO2, MAML1 (Mastermind- like protein 1), TWIST1, and Musashi1 which are involved in the Notch and Wnt signaling pathways play an imperative role in the maintenance and development of CSCs in ESCC. Twist1 and MAML1 act as transcription factors, causing epithelial-mesenchymal transition (EMT) process during tumormetastasis. Moreover, Twist1 is an inhibitor of E-cadherin expression. Musashi1 is a translational inhibitor for Notch and Wnt silencers, Numb and Dickkopf3, prompting to the activation of these pathways. Also, PYGO2 mediates chromatin remodeling complex and transcriptional machinery in Wnt pathway. There are unavoidable similitudes among normal and cancer stem cells; therefore the majority of therapeutic strategies will bring about normal stem cells harm, underlining the need for more particular CSC markers. Various markers such as CD44, ALDH, Pygo2, MAML1, Twist1, Musashi1, CD271 and CD90 are resolved to isolate cells with stem-like characteristics in ESCC. Also, some biomarkers like ALDH1, HIWI, Oct3/4, ABCG2, SOX2, SALL4, BMI-1, NANOG, CD133 and podoplanin identified with the recognizable proof of CSCs can possibly be utilized as prognostic indicators for patients with ESCC. Conclusion: CSCs in esophageal squamous cell carcinoma are mainly responsible for therapy failures and cancer relapses through modulation of intrinsic and/or extrinsic factors so the main objective in cancer treatment modalities is to focus on these special CSC populations. To this point, different cell-surface components, signaling intermediate molecules, survival pathway elements and chromatin modifiers should be the targets for cancer stem cell therapies

Cell and Cancer, Cancer Stem Cells, Stem Cells and Cancer, Solid Tumors, Cancer Treatment and Management, Targeted Cancer Therapy