Conclusion
Our data suggest that smoking cigarettes promoted cancer stem-like cell generation in the head and neck area via the OCT-4/ID1/NF-κB/BMI-1 signaling pathway.
Methods
We used in vitro, in vivo, and archival human HNSCC tissue analysis to evaluate the effects of CSC on cancer stem-like cell formation.
Results
We found that CSC regulated OCT-4 expression, which subsequently regulated ID1 and NF-κB, at the promoter, mRNA, and protein levels in vitro. Furthermore, OCT-4 knockdown with siRNA reduced ID1 expression. ID1 and NF-κB synergistically increased the expression of BMI-1 and stimulated keratinocyte sphere generation. In vivo, ID1 and NF-κB acted together to generate malignant xenograft tumors, which were aggressive locally and systemically metastatic. Clinical data confirmed that ID1- and NF-κB-positive patients had poor clinical outcomes and 5-year disease-free survival.