Abstract
The transcriptional factor SALL4, an important stem cell regulator, is expressed in hematopoietic stem cells and various malignancies, but its role in EGFR-mutated NSCLCs has not been studied yet. Here, we report that the expression of Sal-like protein 4 (SALL4), was significantly higher in EGFR mutated lung tumors than in non-tumor tissue. SALL4-high lung cancer patients had poorer prognosis after surgery than SALL4-low patients. The expression of SALL4 could be induced by the activation of EGFR through the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. The knockdown of SALL4 expression could suppress spheroid formation and the expression of lung cancer stem cell marker CD44. More interestingly, the knockdown of SALL4 expression could suppress the migration, invasion, and metastasis of the lung cancer cells and significantly increase the sensitivity of EGFR mutated cells to Erlotinib. These results suggest that SALL4 may be a novel potential therapeutic target for the diagnosis and treatment of lung cancer.
Highlights
Lung cancer is marked by genetic and histopathological heterogeneity, and remains the leading cause of cancer deaths globally[1]
Sal-like protein 4 (SALL4) expression is significantly correlated with poor survival
To analyze the correlation between the expression of SALL4 and epidermal growth factor receptor (EGFR) mutation, microarray analysis of lung cancer cases was performed and results showed that the SALL4 expression was highest in lung cancer with EGFR mutations among tumor and non-tumor cases (Fig. 1b)
Summary
Lung cancer is marked by genetic and histopathological heterogeneity, and remains the leading cause of cancer deaths globally[1]. The phenotypic diversity of cancer cells has traditionally been explained by changes in genetic and nongenetic factors. The mechanisms underlying tumorigenesis, medicinal resistance, and recurrence are not clearly established. Cancer stem cells may provide a powerful explanation for tumor heterogeneity[2]. There is increasing evidence that cancer is maintained by a subset of tumor cells with stem/progenitor cell characteristics[3]. Recent studies showed that this small subset of tumor cells can generate tumor more efficiently in vivo and less vulnerable to chemo/radiation-resistant than other tumor cells[4]
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