SOX1 promotes tumorigenic capability and chemoresistance via the upregulation of CSF2 in colorectal cancer

Resistance to chemotherapy and cancer relapse are major clinical challenges attributed to a subpopulation of cancer stem cells (CSCs), but the underlying molecular factors require further characterization. Here, we found that chemoresistant patient tumor tissue exhibited higher expression of stemness transcription factors SOX1 and was associated with poorer overall survival in colorectal cancer patients. Overexpressing SOX1 significantly enhanced chemoresistance together with promoting stem cell-like properties in CRC cells, whereas silencing SOX1 had the opposite effects in vitro and in vivo. Mechanistically, SOX1 overexpression activated the NF-KB pathway by interacting with P65. SOX1 promoted the expression of the NF-KB downstream gene, colony-stimulating factor 2 (CSF2), by enhancing the binding of P65 to the promoter region of the CSF2 gene, which is critical for the SOX1 mediated cancer stem-cell phenotype and tumorigenicity. In conclusion, our findings demonstrate that SOX1 upregulated CSF2 to confers cancer stemness traits and chemoresistance, indicating a novel therapeutic strategy for chemoresistant CRC displaying aberrant SOX1 expression.