Evidence map›Paper›PMID 30967626›Full record

ArticleOncogene2019

MST1R kinase accelerates pancreatic cancer progression via effects on both epithelial cells and macrophages.

Michele L Babicky, Megan M Harper, Jeffery Chakedis, Alex Cazes, Evangeline S Mose, Dawn V Jaquish, Randall P French, Betzaira Childers, Hakan Alakus, Michael C Schmid and 11 more

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

Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. RON (Cancers · 2022
    Article
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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

21 authors at 2 institutions in 1 country.

Michele L BabickyDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Megan M HarperDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Jeffery ChakedisDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Alex CazesDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Evangeline S MoseDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Dawn V JaquishDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Randall P FrenchDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Betzaira ChildersDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Hakan AlakusDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Michael C SchmidDepartment of Pathology, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-3445-0013
Phillippe FoubertDepartment of Pathology, University of California, San Diego, La Jolla, CA, 92093, USA.
Jaclyn MiyamotoDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Patrick J HolmanDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Zakkary J WalterscheidDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Chih-Min TangDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.
Nissi VarkiDepartment of Family Medicine and Epidemiology, University of California, San Diego, La Jolla, CA, 92093, USA.
Jason K SicklickDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0003-4403-0271
Karen MesserDepartment of Family Medicine and Epidemiology, University of California, San Diego, La Jolla, CA, 92093, USA.
Judith A VarnerDepartment of Pathology, University of California, San Diego, La Jolla, CA, 92093, USA.
Susan E WaltzDepartment of Cancer Biology, University of Cincinnati College of Medicine, and Research Service, Cincinnati Veteran's Administration Medical Center, Cincinnati, OH, 45267, USA.
Andrew M LowyDivision of Surgical Oncology, Department of Surgery, University of California, San Diego, La Jolla, CA, 92093, USA. alowy@ucsd.edu.
University of California San Diego · USUniversity of Cincinnati Medical Center · US

Funding

UCSD Cancer Center Training Program in Drug DevelopmentT32CA121938 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Bouvet, Dwayne G. Stupack · 2006 to 2026
$10.3M
Role of PI3Kinase in Tumor Progression and MetastasisR01CA167426 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Judith A VARNER · 2012 to 2026
$5.8M
Targeting the innate immune response in HNSCCR01DE027325 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Judith A VARNER · 2017 to 2026
$4.8M
Therapeutic Targeting of Macrophage PI3Kgamma in HNSCCR01CA226909 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kathryn Ann Gold, Judith A VARNER · 2018 to 2026
$3.9M
RON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9M
NCI NIH HHS R01 CA155620NCI NIH HHS R01 CA167426NCI NIH HHS R01 CA226909NCI NIH HHS T32 CA121938NIDCR NIH HHS R01 DE027325
6 · The paper itself

Abstract

The MST1R (RON) kinase is overexpressed in >80% of human pancreatic cancers, but its role in pancreatic carcinogenesis is unknown. In this study, we examined the relevance of Mst1r kinase to Kras driven pancreatic carcinogenesis using genetically engineered mouse models. In the setting of mutant Kras, Mst1r overexpression increased acinar-ductal metaplasia (ADM), accelerated the progression of pancreatic intraepithelial neoplasia (PanIN), and resulted in the accumulation of (mannose receptor C type 1) MRC1+, (arginase 1) Arg+ macrophages in the tumor microenvironment. Conversely, absence of a functional Mst1r kinase slowed PanIN initiation, resulted in smaller tumors, prolonged survival and a reduced tumor-associated macrophage content. Mst1r expression was associated with increased production of its ligand Mst1, and in orthotopic models, suppression of Mst1 expression resulted in reduced tumor size, changes in macrophage polarization and enhanced T cell infiltration. This study demonstrates the functional significance of Mst1r during pancreatic cancer initiation and progression. Further, it provides proof of concept that targeting Mst1r can modulate pancreatic cancer growth and the microenvironment. This study provides further rationale for targeting Mst1r as a therapeutic strategy.

Indexed as

AnimalsCarcinoma, Pancreatic DuctalDisease ProgressionEpithelial CellsFemaleGene Knockdown TechniquesHippo KinasesHumansIntracellular Signaling Peptides and ProteinsMacrophagesMaleMiceMice, Inbred C57BLMice, TransgenicPancreatic NeoplasmsProof of Concept StudyHippo KinasesIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesReceptor Protein-Tyrosine KinasesRON proteinSTK4 protein, human

Identifiers

PMID30967626
PMCPMC6625868
OpenAlexW2939239217

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Registered trials

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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.