SOX2 is a gene that encodes for a transcription factor belonging to the SOX gene family and contains a high-mobility group (HMG) domain, which permits highly specific DNA binding. Consequently, SOX2 functions as an activator or suppressor of gene transcription. SOX2 has been described as an essential embryonic stem cell gene and moreover, a necessary factor for induced cellular reprogramming. SOX2 research has only recently switched focus from embryogenesis and development to SOX2’s function in disease. Particularly, the role of SOX2 in cancer pathogenesis has become of interest in the field. To date, studies have shown SOX2 to be amplified in various cancer types and affect cancer cell physiology via involvement in complicated cell signaling and protein-protein interactions. Recent reviews in this field have highlighted SOX2 in mammalian physiology, development and pathology. In this review, we comprehensively compile what is known to date about SOX2’s involvement in cancer biology, focusing on the most recent findings in the fields of cellular signaling and cancer stem cells. Lastly, we underscore the role of SOX2 in the clinic and highlight new findings, which may provide novel clinical applications for SOX2 as a prognostic marker, indicator of metastasis, biomarker or potential therapeutic target in some cancer types.

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SOX2 and cancer: current research and its implications in the clinic.

Cancer stem cells (CSCs), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute towards a 'stemness' phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers and signaling pathways.

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Stemness-Related Markers in Cancer.

SALL4, the missing link between stem cells, development and cancer.

https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=4913&context=open_access_pubs

A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells

SALL4: an emerging cancer biomarker and target.

Cancer stem cells, as a subgroup of tumor cells, resemble critical properties of embryonic stem cells (ESCs) such as self-renewal and maintenance of stemness state. SALL4 and SOX2 are two main transcription factors involving in maintenance of pluripotency, self-renewal and cell fate decision in ESCs. In this study, we aimed to elucidate the expression levels of these important transcription factors in esophageal squamous cell carcinoma (ESCC) and to reveal their probable roles in maintenance and progression of the disease. The expression level of SALL4 and SOX2 was analyzed in fresh tumoral tissues in comparison with distant tumor-free tissues of 50 ESCC patients by relative comparative real-time PCR. SALL4 and SOX2 were overexpressed in 64 and 32 % of tumor samples, respectively, in significant correlation with each other (p = 0.028). There was a significantly inverse correlation between low level of SALL4 expression and metastasis of tumor cells into the lymph nodes (p = 0.035). Furthermore, co-overexpression of the genes was significantly correlated with the depth of tumor invasion (p = 0.045) and metastasis to the lymph nodes (p = 0.049). SALL4 and SOX2 are co-overexpressed in ESCC and have a significant correlation with invasion and metastasis of the disease. To the best of our knowledge, this is the first report of SALL4 clinical relevance in ESCC to date. The clinical consequences of SALL4–SOX2 association suggest a possible functional interaction between these factors in regulation of ESCC maintenance and aggressiveness and introduce these regulators of stemness state as potentially interesting therapeutic targets to bring new opportunities for onco-therapeutic modalities.

Afsaneh Javdani-Mallak

Papers

Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma