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.
Early detection of CRC is directly correlated to improved outcomes, increased survival rates and reduced mortality. Our results can introduce SALL4 as a critical biomarker for efficient screening of patients to detect early stages of CRC.
Epithelial-mesenchymal transition (EMT) is crucial for specific morphogenetic movements during embryonic development as well as pathological processes of tumor cell invasion and metastasis. TWIST and SNAIL play vital roles in both developmental and pathological EMT. Our aim in this study was to investigate the functional correlation between TWIST1 and SNAIL in human ESCC cell line (KYSE-30). The packaging cell line GP293T was cotransfected with either control retroviral pruf-IRES-GFP plasmid or pruf-IRES-GFP-hTWIST1 and pGP plasmid. The KYSE-30 ESCC cells were transduced with produced viral particles and examined with inverted fluorescence microscope. DNA was extracted from transduced KYSE-30 cells and analyzed for copy number of integrated retroviral sequences in the target cell genome. The concentration of retroviral particles was determined by Real-time PCR. After RNA extraction and cDNA synthesis, the mRNA expression of TWIST1 and SNAIL was assessed by comparative real-time PCR amplification. Ectopic expression of TWIST1 in KYSE-30, dramatically reduces SNAIL expression. Retroviral transduction enforced TWIST1 overexpression in GFP-hTWIST1 nearly 9 folds in comparison with GFP control cells, and interestingly, this TWIST1 enforced expression caused a - 7 fold decrease of SNAIL mRNA expression in GFP-hTWIST1 compared to GFP control cells. Inverse correlation of TWIST1 and SNAIL mRNA levels may introduce novel molecular gene expression pathway controlling EMT process during ESCC aggressiveness and tumorigenesis. Consequently, these data extend the spectrum of biological activities of TWIST1 and propose that therapeutic repression of TWIST1 may be an effective strategy to inhibit cancer cell invasion and metastasis.
SALL4, as a stemness marker, plays a key role in the maintenance of pluripotency and self‐renewal of cancer stem cells. To elucidate probable linkage between SALL4 stemness marker and bone morphogenetic protein (BMP) cell signaling pathway, we aimed to analyze the expression levels of the related genes in esophageal squamous cell carcinoma (ESCC) patients. Tumoral and corresponding margin normal tissues from 50 treatment‐naive ESCC patients were subjected for expression analysis using relative comparative real‐time reverse transcription polymerase chain reaction. There were significant correlations between SALL4 mRNA and BMP signaling target genes expression including SIZN1, VENTX, and DIDO1 (P < 0.01). Tight associations of gene expression were observed in primary stages of tumor progression (stages I/II), and the invaded tumors to the adventitia (T3/T4). Furthermore, significant correlations between the expression of BMP signaling target genes were observed (P < 0.01). SALL4 may play role in tumorigenesis and tumor cell invasiveness of ESCC through correlation with BMP signaling genes.
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