Evidence map›Paper›PMID 37163116›Full record

ArticlebioRxiv : the preprint server for biology2023

Bcl-xL is translocated to the nucleus via CtBP2 to epigenetically promote metastasis.

Tiantian Zhang, Sha Li, Yingcai Adrian Tan, Joseph HyungJoon Na, Zhengming Chen, Priyadarshan Damle, Xiang Chen, Soyoung Choi, Bikash Mishra, Dunrui Wang and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 1 country.

Tiantian ZhangDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Sha LiDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Yingcai Adrian TanGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
Joseph HyungJoon NaDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Zhengming ChenDivision of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, NY 10065, USA.
Priyadarshan DamleDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Xiang ChenDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Soyoung ChoiDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Bikash MishraImmunology & Microbial Pathogenesis Graduate Program, Weill Cornell Medicine, New York, NY 10065, USA.
Dunrui WangLaboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Steven R GrossmanUSC Norris Comprehensive Cancer Center and Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Xuejun JiangCell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Yi LiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Yao-Tseng ChenDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Jenny Z XiangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
Yi-Chieh Nancy DuDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Cornell University · USBaylor College of Medicine · USMemorial Sloan Kettering Cancer Center · USNational Institutes of Health · USUniversity of Southern California · USVirginia Commonwealth University · US

Funding

Beyond apoptosis, Bcl-xL in tumor metastasisR01CA204916 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI DU, YI-CHIEH NANCY · 2017 to 2021
$2.0M
NCI NIH HHS R01 CA204916
6 · The paper itself

Abstract

Besides its mitochondria-based anti-apoptotic role, Bcl-xL also travels to the nucleus to promote cancer metastasis by upregulating global histone H3 trimethyl Lys4 (H3K4me3) and TGFβ transcription. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates H3K4me3 modification are not understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus. Knockdown of CtBP2 by shRNA decreases the nuclear portion of Bcl-xL and reverses Bcl-xL-induced cell migration and metastasis in mouse models. Furthermore, knockout of CtBP2 suppresses Bcl-xL transcription. The binding between Bcl-xL and CtBP2 is required for their interaction with MLL1, a histone H3K4 methyltransferase. Pharmacologic inhibition of MLL1 enzymatic activity reverses Bcl-xL-induced H3K4me3 and TGFβ mRNA upregulation as well as cell invasion. Moreover, cleavage under targets and release using nuclease (CUT&RUN) coupled with next generation sequencing reveals that H3K4me3 modifications are particularly enriched in the promotor region of genes encoding TGFβ and its signaling pathway in the cancer cells overexpressing Bcl-xL. Altogether, the metastatic function of Bcl-xL is mediated by its interaction with CtBP2 and MLL1.

Indexed as

Bcl-xLCtBP2epigenetic modificationmetastasisMLL1

Identifiers

PMID37163116
PMCPMC10168309
OpenAlexW4367300980

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.