LRP6 aggravates proliferation, invasion, and immunosuppression in diffuse large B-cell lymphoma: a novel prognostic...

Low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) has been found to be highly expressed in various solid tumors, correlating with malignant phenotypes and poor prognosis. However, the role of LRP6 in diffuse large B cell lymphoma (DLBCL) remains unclear. In this study, we revealed that LRP6 expression was significantly elevated in DLBCL patients. High expression of LRP6 is not only associated with tumor subtype, Ann Arbor stage, and extra-nodal invasion, but also with poor prognosis. The knockout of LRP6 significantly inhibited cell proliferation and migration, induced cell cycle arrest, and promoted apoptosis in DLBCL cells. Mechanistically, LRP6 knockout inhibited both the Wnt/β-catenin and mTORC1 signaling pathways. Furthermore, we found that LRP6 knockout reduced the expression of indoleamine 2,3-dioxygenase 1 (IDO1), a negative regulator within the tumor microenvironment (TME), and consequently decreased the level of kynurenine (KYN), indicating a reduction in IDO1 enzymatic activity. Additionally, LRP6 knockout suppressed DLBCL xenograft tumor growth. Collectively, our findings suggested that high LRP6 expression in DLBCL patients was associated with poor prognosis, and LRP6 contributes to DLBCL progression and immunosuppression. Taken together, these findings highlight LRP6 as a potential novel prognostic biomarker and therapeutic target.