Target | Pathway | Cell line or HCC model | Pro-tumor Results |
---|---|---|---|
RIPK3 and FAO | ROS-caspase1-PPAR pathway | Murine H22 cells and C57BL/6 WT mice injected with diethylnitrosamine as HCC model | The RIPK3-FAO-ROS-caspase1-PPAR signaling axis is responsible for increased M2-TAM infiltration, which promotes HCC tumorigenesis [106]. |
LINC00662 | WNT3A-Wnt/b-catenin signaling | HCCLM3, MHCC97H, Huh7, SK-HEP-1, and Hepa1–6 HCC cells | By upregulating WNT3A expression, LINC00662 activates the Wnt/b-catenin pathway and then induces M2 macrophage polarization, contributing to HCC tumorigenesis and invasion and repressing HCC cell apoptosis [107, 108]. |
IL-25 | / | Human HCC cell lines MHCC97L and HepG2 cells; Murine HCC cell lines H22, and Hepa1–6; and BALB/c nude mice with the portal venous injection macrophages as HCC model. | IL-25 facilitates M2 TAM (CD206/CD68) infiltration, promotes secretion of the chemokine CXCL-10, and then induces HCC progression through the EMT pathway [109]. |
CAF-induced endosialin | Interaction with CD68 and regulate GAS6 expression in CAF | Huh7 cell HFL-1 cells | In CAFs, via an interaction with CD68, endosialin promotes the expression of GSA6, which results in increased M2 macrophages recruitment and HCC progression [110]. |
HCC-derived HMGB1 | ROS-TLR2-NOX2-autophagy axis | Mouse hepatoma cell line ML-14a cells and murine in a situ hepatoma model | Hepatoma-derived HMGB1 stimulates ROS via the TLR2/NOX2 axis, thereby inducing M2 macrophage polarization and subsequently supporting HCC growth [111]. |
Nogo-B | Nogo-B-Yap/Taz pathway | Murine HCC cell lines Hepa1–6 cells and H22 cells, macrophage cell line RAW 264.7 cells | Elevated Nogo-B expression facilitates M2 TAM polarization and promotes HCC tumor growth in vivo by inducing Yap/Taz signaling [112]. |