Fig. 9: A schematic mechanism underlying interactions between primary CRC cells and distal fibroblasts through the EVs-mediated transfer of ITGBL1 in promoting the metastasic niche formation in lung and liver. | Nature Communications

Fig. 9: A schematic mechanism underlying interactions between primary CRC cells and distal fibroblasts through the EVs-mediated transfer of ITGBL1 in promoting the metastasic niche formation in lung and liver.

From: Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation

Fig. 9

In detail, for biological function description, tumor-derived ITGBL1-enriched EVs convert primary fibroblasts to CAFs via binding to TNFAIP3 and activating the NF-κB signaling pathway. The ITGBL1-activated CAFs promote CRC stemness, aggressiveness, and EMT by pro-inflammatory cytokines, such as IL-6 and IL-8. CAFs manipulated the TME to support metastatic tumor growth. For the molecular mechanism of ITGBL1 secretion, in primary CRC, the transcription of ITGBL1 was regulated by RUNX2, and the secretion of ITGBL1-loaded EVs was elevated by RUNX2 through the ceramide-dependent EVs secretion pathways mediated by nSMase2.

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