Schematic diagram indicating the mechanisms by which SPRED2 regulates the stemness of HCC cells. (IMAGE)

China Anti-Cancer Association

Schematic diagram indicating the mechanisms by which SPRED2 regulates the stemness of HCC cells.

Caption

Schematic diagram indicating the mechanisms by which SPRED2 regulates the stemness of HCC cells. miR-506-3p downregulates KLF4 expression. Left panel: Under normal conditions, SPRED2 binds to RAF and/or RSK2 and inhibits the ERK signaling pathway. SPRED2 also binds to DYRK1A and inhibits the STAT3 signaling pathway. As a result, the inhibitory effect on miR-506-3p is negated, resulting in increased expression of miR-506. SPRED2 also forms a protein complex with p53 and directly promotes miR-506-3p expression. Thus, SPRED2 coordinates all three pathways (ERK, STAT3, and p53) to increase miR-506-3p expression, thereby reducing KLF4 expression and cell stemness in HCC cells. Right panel: When HCC cells lose the expression of SPRED2, the ERK and STAT3 pathways are no longer inhibited and the formation of SPRED2/p53 protein complex decreases, leading to decreased miR-506-3p expression. This results in increased KLF4 expression and promotion of HCC stemness.

Credit

Cancer Biology & Medicine

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