Further mechanistic studies revealed that POU2F2 was a crucial transcription factor mediating MIF-driven activation of SPP1<sup>+</sup>TAMs, and that BCL9L was a direct downstream target of POU2F2.<h4>Conclusions</h4>Our findings suggest that the MIF/CD44/POU2F2/BCL9L signaling axis is involved in the proangiogenic capacity of activated SPP1<sup>+</sup>TAMs, thereby enhances CRC metastasis. Here, CD44 is linked to colorectal carcinoma.