ArticleMolecular cancer2026
CDK6/4 inactivates BAP1 deubiquitinase destabilizing VHL to promote metastatic colonization in liver.
Article in Molecular cancer, 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
13 authors.
Funding
Abstract
backgroundSingle organ metastasis to liver typically occurs in uveal melanoma (UM) and colorectal carcinoma (CRC). Colonization in the host organ is a beachhead step of the metastasis process. The governing pathways of the seeding cells are far away clarified.
objectiveThis study aimed at deciphering governing pathways of the seeding cells that required for metastatic colonization and developing novel strategies against metastasis.
designMass spectrum analysis of Co-IP pellets was applied to identify the kinase and the substrates of BAP1. Findings were further validated using GST-pull down assay and the proximity ligation assay. The function of CDK6/4-BAP1-VHL signaling axis in promoting liver metastasis was investigated by UM and CRC mouse model.
resultsMass spectrum analysis of Co-IP pellets with anti-BAP1 revealed that VHL bound with BAP1. Their physical interaction was further confirmed by GST-pull down assay and proximity ligation assay. We mapped the interacting domains between BAP1 and VHL. In vivo ubiquination assay showed that BAP1 deubiquitinated VHL at K48-linked poly-ubiquitin chain and stabilized VHL protein. Further, exosomal CDK6/4 serine/threonine kinases were identified to phosphorylate BAP1 at S369 to inactivate BAP deubiquitinationase, forming CDK6/4-BAP1-VHL signaling axis. Functionally, BAP1 inhibited CSCs, EMT and metastatic colonization to liver in uveal melanoma and colorectal carcinoma via upregulating VHL protein, which was, however, reversed by targeting CDK6/4.
conclusionIn conclusion, VHL is a novel substrate of BAP; and BAP1 suppresses CSCs and metastatic colonization to liver via substrate VHL. These findings may shed lights on the mystery substrates of BAP1 and the underlying mechanism of colonization in liver and intervention targets.
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.