Could gastrointestinal tumor-initiating cells originate from cell-cell fusion ?

Tumor-initiating cells (TICs) or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation, progression, metastasis, and drug resistance. It is hypothesized that gastrointestinal TICs (giTICs) might originate from cell-cell fusion. Here, we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both and . We review giTICs that are capable of initiating tumors with 5000 or fewer fused cells. Under this restriction, there is currently little evidence demonstrating that giTICs originate from cell-cell fusion . However, there are many reports showing that tumor generation occurs with more than 5000 fused cells. In addition, the mechanisms of giTIC generation cell-cell fusion are poorly understood, and thus, we propose its potential mechanisms of action. We suggest that future research should focus on giTIC origination from cell-cell fusion isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less fused cells, and further clarification of the underlying mechanisms. Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.