Fig. 9

Graphic summary. In the absence of APN, hypoxia stabilized HIF1α increases SCF production. Secreted SCF activates STAT3, which is involved in HIF1α transcription (blue line arrow). In the presence of APN, HIF1α is degraded via activation of the AdipoR/GSK3β axis, which prevents amplification of the HIF1α signaling pathway (red line arrow). This implies that APN acts as a breaker in HIF1α amplification. On the other hand, HIF1α stimulates CD44 expression, and CD44-expressing BMSCs move into an HA-rich EL-4 tumor mass, in which BMSCs secrete CCL8 to recruit CD8⁺ T cells. This pathway contributes to the inhibition of tumor growth