Together, this study uncovering Skp2-mediated Twist stabilization and oncogenic functions in CRPC offers new knowledge on how CRPC progresses and acquires chemoresistance during tumor progression.
Our results not only reveal the molecular mechanism by which mechanical cues induce Skp2 transcription, but also uncover a role for YAP-Skp2 oncogenic signaling in the relationship between tissue rigidity and cancer progression.
Flavokawain A induces deNEDDylation and Skp2 degradation leading to inhibition of tumorigenesis and cancer progression in the TRAMP transgenic mouse model.
The F-box protein Skp2, a component of the SCF (Skp1-Cullin 1-F-box) E3 ubiquitin-ligase complex, has been shown to regulate cellular proliferation, cancer progression and metastasis by targeting several cell cycle regulators for ubiquitination and subsequent 26S proteasome degradation.
These data demonstrate that S-phase kinase-associated protein 2 expression is closely linked to tumor progression and represents an independent predictor of poor prognosis in hepatocellular carcinoma.
The expression of SKP2, p27 and phospho-MAPK/ERK1/2 were strongly associated with cervical neoplastic progression (P<0.0001, P=0.006, P=0.003, respectively; Fisher's Exact Test).