Evidence map›Paper›PMID 37942963›Full record

ArticleCell cycle (Georgetown, Tex.)2023

Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.

M C Rowell, X Deschênes-Simard, S Lopes-Paciencia, B Le Calvé, P Kalegari, L Mignacca, A Fernandez-Ruiz, J Guillon, F Lessard, V Bourdeau and 8 more

Open access · greenAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

12 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

18 authors at 5 institutions in 3 countries.

M C RowellDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
X Deschênes-SimardDépartement de Biochimie et Médecine Moléculaire, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada.
S Lopes-PacienciaDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
B Le CalvéDépartement de Biochimie et Médecine Moléculaire, Université de Montréal, QC, Canada.
P KalegariDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
L MignaccaDépartement de Biochimie et Médecine Moléculaire, Université de Montréal, QC, Canada.
A Fernandez-RuizDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
J GuillonDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
F LessardDépartement de Biochimie et Médecine Moléculaire, Université de Montréal, QC, Canada.
V BourdeauDépartement de Biochimie et Médecine Moléculaire, Université de Montréal, QC, Canada.
S IgelmannDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
A M DumanDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
Y StanomDépartement de Biochimie et Médecine Moléculaire, Université de Montréal, QC, Canada.
F KottakisMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
V DeshpandeMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
V KrizhanovskyDepartment of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
N BardeesyMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
G FerbeyreDépartement de Biochimie et Médecine Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.ORCID 0000-0002-2146-618X
Centre Hospitalier de l’Université de Montréal · CAUniversité de Montréal · CAHarvard University · USHôpital Maisonneuve-Rosemont · CAWeizmann Institute of Science · IL

Funding

The RAS and P13K Pathways in Pancreatic AdenocarcinomaP01CA117969 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KALLURI, RAGHU · 2006 to 2025
$41.7M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI SHIVDASANI, RAMESH A · 2007 to 2023
$33.2M
Functions of the LKB1 tumor suppressor in control in metabolism and epigenticsR01CA215498 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI EL-BARDEESY, NABEEL · 2018 to 2022
$2.7M
European Research CouncilNCI NIH HHS P01 CA117969NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA215498
6 · The paper itself

Abstract

Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that stimulate the ERK pathway. Aberrantly high ERK activation triggers oncogene-induced senescence, which halts tumor progression. Here we report that low-grade pancreatic intraepithelial neoplasia displays very high levels of phospho-ERK consistent with a senescence response. However, advanced lesions that have circumvented the senescence barrier exhibit lower phospho-ERK levels. Restoring ERK hyperactivation in PDAC using activated RAF leads to ERK-dependent growth arrest with senescence biomarkers. ERK-dependent senescence in PDAC was characterized by a nucleolar stress response including a selective depletion of nucleolar phosphoproteins and intranucleolar foci containing RNA polymerase I designated as senescence-associated nucleolar foci (SANF). Accordingly, combining ribosome biogenesis inhibitors with ERK hyperactivation reinforced the senescence response in PDAC cells. Notably, comparable mechanisms were observed upon treatment with the platinum-based chemotherapy regimen FOLFIRINOX, currently a first-line treatment option for PDAC. We thus suggest that drugs targeting ribosome biogenesis can improve the senescence anticancer response in pancreatic cancer.

Indexed as

Carcinoma, Pancreatic DuctalPancreatic NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCellular SenescenceHumansMAP Kinase Signaling SystemRibosomesfolfirinoxMAP kinasenucleoluspancreatic cancerribosome biogenesistherapy-induced senescence

Identifiers

PMID37942963
PMCPMC10732607
OpenAlexW4388526813

What OpenQuestion holds

Textmetadata
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.