Evidence map›Paper›PMID 33755595›Full record

ArticleJCI insight2021

LIN28B induces a differentiation program through CDX2 in colon cancer.

Kensuke Suzuki, Yasunori Masuike, Rei Mizuno, Uma M Sachdeva, Priya Chatterji, Sarah F Andres, Wenping Sun, Andres J Klein-Szanto, Sepideh Besharati, Helen E Remotti and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
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

11 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 8 institutions in 2 countries.

Kensuke SuzukiHerbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Disease, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA.
Yasunori MasuikeHerbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Disease, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA.
Rei MizunoDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Uma M SachdevaDivision of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
Priya ChatterjiBroad Institute of MIT and Harvard University, Cambridge, Massachusetts, USA.
Sarah F AndresPapé Family Pediatric Research Institute, Oregon Health & Science University, Portland, Oregon, USA.
Wenping SunInstitute for Biomedical informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Andres J Klein-SzantoHistopathology Facility and Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Sepideh BesharatiDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
Helen E RemottiDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
Michael P VerziDepartment of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey, USA.
Anil K RustgiHerbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Disease, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA.
Columbia University Irving Medical Center · USBroad Institute · USFox Chase Cancer Center · USKyoto University · JPMassachusetts General Hospital · USOregon Health & Science University · USRutgers, The State University of New Jersey · USUniversity City Science Center · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
NCI NIH HHS P30 CA013696
6 · The paper itself

Abstract

Most colorectal cancers (CRCs) are moderately differentiated or well differentiated, a status that is preserved even in metastatic tumors. However, the molecular mechanisms underlying CRC differentiation remain to be elucidated. Herein, we unravel a potentially novel posttranscriptional regulatory mechanism via a LIN28B/CDX2 signaling axis that plays a critical role in mediating CRC differentiation. Owing to a large number of mRNA targets, the mRNA-binding protein LIN28B has diverse functions in development, metabolism, tissue regeneration, and tumorigenesis. Our RNA-binding protein IP (RIP) assay revealed that LIN28B directly binds CDX2 mRNA, which is a pivotal homeobox transcription factor in normal intestinal epithelial cell identity and differentiation. Furthermore, LIN28B overexpression resulted in enhanced CDX2 expression to promote differentiation in subcutaneous xenograft tumors generated from CRC cells and metastatic tumor colonization through mesenchymal-epithelial transition in CRC liver metastasis mouse models. A ChIP sequence for CDX2 identified α-methylacyl-CoA racemase (AMACR) as a potentially novel transcriptional target of CDX2 in the context of LIN28B overexpression. We also found that AMACR enhanced intestinal alkaline phosphatase activity, which is known as a key component of intestinal differentiation, through the upregulation of butyric acid. Overall, we demonstrated that LIN28B promotes CRC differentiation through the CDX2/AMACR axis.

Indexed as

AdenocarcinomaAnimalsCaco-2 CellsCDX2 Transcription FactorCell DifferentiationCell Line, TumorColorectal NeoplasmsEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHCT116 CellsHumansLiver NeoplasmsMiceMice, TransgenicNeoplasm TransplantationRacemases and Epimerasesalpha-methylacyl-CoA racemaseCDX2 Transcription FactorLIN28B protein, humanLin28b protein, mouseRacemases and EpimerasesRNA-Binding ProteinsCell BiologyColorectal cancerGastroenterologyMolecular biology

Identifiers

PMID33755595
PMCPMC8262288
OpenAlexW3137349789

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.