ArticleCell death & disease2026
TSC22D4 drives clear cell renal cell carcinoma progression and therapy resistance by stabilizing NRF2 through KEAP1 disruption.
Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is highly aggressive and difficult to manage due to its intrinsic resistance to oxidative stress. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of oxidative stress responses, is frequently overexpressed in ccRCC and is associated with poor prognosis. NRF2 promotes tumor progression by driving proliferation, metabolic reprogramming, and ferroptosis resistance; however, the upstream mechanisms controlling NRF2 stability remain incompletely understood. Here, we identify TSC22 domain family member 4 (TSC22D4) as a Kelch-like ECH-associated protein 1 (KEAP1)-interacting protein that directly binds to KEAP1 via a conserved ETGE motif. This interaction disrupts the KEAP1-NRF2 complex, preventing NRF2 ubiquitination and degradation, thereby enhancing NRF2 stability and activating antioxidant response element (ARE)-driven transcription. Notably, TSC22D4 upregulates solute carrier family 7 member 11 (SLC7A11), thereby suppressing ferroptosis and conferring resistance to sorafenib in ccRCC. TSC22D4 is markedly overexpressed in ccRCC and promotes tumor cell proliferation, invasion, and metastasis. Clinically, elevated TSC22D4 expression correlates with advanced disease stage and poor patient survival. In conclusion, TSC22D4 promotes ccRCC progression and sorafenib resistance by activating the KEAP1-NRF2-SLC7A11 axis and suppressing ferroptosis, highlighting TSC22D4 as a potential therapeutic target in ccRCC.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.