By targeting β-catenin, β-TRCP1 plays a negative role in regulating the Wnt pathway, partially explaining how somatic mutations in β-TRCP1/2 preventing their E3 ligase activity identified in human gastric cancer correlated with stabilization of β-catenin in these tissues and development of tumors (Saitoh and Katoh, 2001).
WA inhibits catalytic β-subunit of 20S proteasome core particle similarly to the clinically used proteasome inhibitor (PI) bortezomib and was shown to impede NF- κB function in cancer cells via stabilization of I κB α, the cytoplasmic inhibitor of NF- κB.
The feasibility of large-scale ex vivo generation of DCs from patients' monocytes allows for therapeutic application of ex vivo-cultured DCs to bypass the dysfunction of endogenous DCs, restore immune surveillance, induce cancer regression and stabilization, and delay or prevent its recurrence.
Loss-of-function mutations in APC or mutations in β-catenin at the phosphorylation site, which are found in almost all human colorectal cancers, lead to stabilization of the β-catenin protein and aberrant activation of Wnt/ β-catenin signaling.
In the future, it will be important to define the calpain-1 target/s involved in filopodia stabilization in cancer cells.
Furthermore, we provide evidence that haemanthamine and other Amaryllidaceae alkaloids also inhibit specifically ribosome biogenesis, triggering nucleolar stress response and leading to p53 stabilization in cancer cells.
These effects have important implications as succinate dehydrogenase (SDH) inactivation and isocitrate dehydrogenase (IDH) neomorphic gain-of-function leading to accumulation of succinate and 2-hydroxyglutarate, respectively, contribute to HIF1α stabilization and cancer promotion [136].
Recently, IL-24 was reported to induce its own expression in cancer cells through mRNA stabilization [38].
Some activating mutations of FGFR3, including the common mutations found in bladder cancer, act by constitutive stabilization of receptor dimers.
Cancer remission and disease stabilization have been demonstrated in cancer patients (de Bono et al. 2000; Engelhardt et al. 1991; Goto et al. 1996; Otto et al. 1996).
