STAB1 Promotes Acute Myeloid Leukemia Progression by Activating the IKK/NF-κB Pathway and Increasing M2 Macrophage Polarization.

As a multifunctional scavenger receptor, stabilin-1 (STAB1) has been identified to induce chronic inflammation and promote cancer progression. Although in silico studies from multiple data sets showed that STAB1 might facilitate the progression of acute myeloid leukemia (AML) and drug resistance, the real impacts of STAB1 expression on AML patients and the detailed mechanisms remain unclear. Herein, we found that a higher expression of STAB1 is associated with a worse prognosis in AML patients. Subsequent in vitro experiments demonstrated that STAB1 knockdown suppressed proliferation and promoted apoptosis through regulating the IKK/NF-κB pathway in human AML cell lines HEL and NB4. In addition, in vivo studies showed that STAB1 silencing prolonged survival, reduced proliferation, and inhibited aggressiveness of AML cells in xenograft mouse models. Moreover, we investigated the impact of STAB1 expression in AML cells on macrophage differentiation and found that co-culture of macrophages with conditioned medium from STAB1-knockdown AML cells reduced M2 polarization of macrophages. Taken together, our study suggests that STAB1 promotes growth and aggressiveness of AML cells through activating the IKK/NF-κB pathway while also regulating M2 macrophage polarization within the chronic inflammatory environment. Therefore, targeting STAB1 could be a potential therapeutic strategy for treating AML.