RNA-Seq V2 level 3 data from 279 tumor samples along with 37 adjacent normal samples from patients enrolled in the The Cancer Genome Atlas (TCGA)-HNSCC study were used to identify upregulated genes using two methods (altered KEAP1-NRF2-CUL3 versus normal, and altered KEAP1-NRF2-CUL3 versus wild-type).
The Speckle-type POZ protein (SPOP) is a member of the MATH-BTB protein family and is a type of joint molecule for Cullin-3.SPOP inhibits tumor growth.
Furthermore, ACLY inhibitor SB-204990 greatly abolishes the promoting effect of CUL3 down-regulation on lipid synthesis, cell proliferation, and tumor growth.
Alterations in nuclear factor (erythroid-derived 2)-like 2, Kelch-like erythroid-derived cap-n-collar homology-associated protein 1, and cullin 3, components of an oxidative stress response pathway, have been recently recognized in some sporadic papillary tumors as well as in fumarate hydratase-deficient tumor and may serve as additional therapeutic targets.
This study identifies many novel candidate genetic drivers of lung cancer and demonstrates that CUL3 acts as a tumor suppressor by regulating oxidative stress.
Cul3 immunohistochemical protein patterns performed on bladder tumours spotted onto tissue microarrays (n = 284), were associated with tumor staging, lymph node metastasis and disease-specific survival.
The expression of Cul3 during hepatic differentiation therefore safeguards against the formation of progenitor cells that carry a great potential for transformation into tumor-initiating cells.