Figure 1: BAFF-induced activation of NF-κB signaling and increased expression of proinflammatory cytokines as procachectic mediators. BAFF interacts with three receptors from the TNF ligand/receptor superfamily, BAFF-R, TACI, and (with lower affinity) BCMA [8]. Upon activation, BCMA signal transduction goes through TNF receptor associated factors (TRAFs) 5 and 6 [96], whereas TACI signals through TRAF2, TRAF5, and TRAF6 [97]. TRAF2 and TRAF5 activate IκB kinase (IKK) via TAK-1 kinase (the canonical NF-κB pathway) [98]. Follow-up phosphorylation of NF-κB inhibitor alpha (IκBα) induces ubiquitination of IκBα and its proteasome degradation [99]. In this way, IκBα is released from the phosphorylated heterodimer p50-p65, and p50-p65 then migrates to the nucleus [99]. BAFF-R signaling starts with TRAF2 and TRAF3 degradation and accumulation of NF-κB inducing kinase (NIK) [100]. In this noncanonical NF-κB pathway, NIK phosphorylates inhibitor of NF-κB kinase alpha (IKKα) [101]. IKKα then induces cleavage of p100 protein in the p100-RelB complex into a p52-RelB complex which acts as a modulator of nuclear gene transcription [102]. Both canonical and noncanonical NF-κB pathways regulate the expression of genes encoding IL-1β [63, 64], IL-2 [65], IL-6 [66, 67], and TNF-α [68]. Proinflammatory cytokines participate in manifestation of cancer cachexia symptoms such as insulin resistance [103], fever [104], inflammation [105], and muscle [106108] and fat tissue wasting [105, 109, 110].