We also modulate the expression of CMKLR1 in HCC cells, and found that CMKLR1 knockdown resulted in elevated expression of PTEN in the absence of chemerin (Fig. 4d), associated with weakened ubiquitination of PTEN, elevated PTEN activity, decreased p-Akt (Ser473) level, and suppressed migration and invasion of HCC cells, indicating that PTEN released from CMKLR1 is less ubiquitinated and more active (Fig. 4d–f, Supplementary Figure S4E). Here, RARRES2 is linked to hepatocellular carcinoma.