Evidence map›Paper›PMID 27180906›Full record

ArticleCell2016

SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b.

Sita Kugel, Carlos Sebastián, Julien Fitamant, Kenneth N Ross, Supriya K Saha, Esha Jain, Adrianne Gladden, Kshitij S Arora, Yasutaka Kato, Miguel N Rivera and 6 more

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

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.

0numbers the graph read from it
0cells of the map it votes in
184citing papers in PubMed
19.2field-weighted citation impact, top 1% 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

184 citing papers in PubMed, 320 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. PARPi Combining Nanoparticle LIN28B siRNA for the Management of Malignant Ascites.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  13. Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025
    Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

124 more citing papers are in PubMed but not listed here.

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

16 authors at 3 institutions in 1 country.

Sita KugelThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Carlos SebastiánThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Julien FitamantThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Kenneth N RossThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Supriya K SahaThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Esha JainThe MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Adrianne GladdenBroad Technology Labs (BTL), The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Kshitij S AroraThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Yasutaka KatoThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Miguel N RiveraThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Sridhar RamaswamyThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Ruslan I SadreyevDepartment of Molecular Biology, The Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Alon GorenBroad Technology Labs (BTL), The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Vikram DeshpandeThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Nabeel BardeesyThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
Raul MostoslavskyThe Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: rmostoslavsky@mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USBroad Institute · US

Funding

The RAS and P13K Pathways in Pancreatic AdenocarcinomaP01CA117969 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DEPINHO, RONALD ANTHONY · 2006 to 2025
$41.7M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
The Role of SIRT6 and Metabolism in APC Mediated TumorigenesisR01CA175727 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MOSTOSLAVSKY, GUSTAVO, MOSTOSLAVSKY, RAUL · 2014 to 2018
$2.6M
TGF-beta Signaling in Pancreatic CancerR01CA133557 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI EL-BARDEESY, NABEEL · 2008 to 2013
$1.7M
Novel targeted therapies for isocitrate dehydrogenase mutantcholangiocarcinomaK08CA194268 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SAHA, SUPRIYA K · 2015 to 2019
$866k
Deciphering SIRT6-dependent metabolic liabilities in Pancreatic cancerR21CA198109 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MOSTOSLAVSKY, RAUL · 2015 to 2016
$390k
NCI NIH HHS K08 CA194268NCI NIH HHS P01 CA117969NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA133557NCI NIH HHS R01 CA175727NCI NIH HHS R21 CA198109
6 · The paper itself

Abstract

Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD(+)-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This epigenetic program defines a distinct subset with a poor prognosis, representing 30%-40% of human PDAC, characterized by reduced SIRT6 expression and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor and uncover the Lin28b pathway as a potential therapeutic target in a molecularly defined PDAC subset. PAPERCLIP.

Indexed as

Gene Expression Regulation, NeoplasticAcetylationAdenocarcinomaAnimalsCell Line, TumorChromatin Assembly and DisassemblyEpigenesis, GeneticFemaleGenes, rasHistonesHumansMaleMiceMice, KnockoutPancreatic NeoplasmsRNA-Binding ProteinsHistonesLIN28B protein, humanRNA-Binding ProteinsSIRT6 protein, humanSirtuinsTumor Suppressor Proteins

Identifiers

PMID27180906
PMCPMC4892983
OpenAlexW2374078013

What OpenQuestion holds

Textmetadata
LicenceTDM
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.