Evidence map›Paper›PMID 30332649›Full record

ArticleCell reports2018

Cdh1 and Pik3ca Mutations Cooperate to Induce Immune-Related Invasive Lobular Carcinoma of the Breast.

Yeji An, Jessica R Adams, Daniel P Hollern, Anthony Zhao, Stephen G Chang, Miki S Gams, Philip E D Chung, Xiaping He, Rhea Jangra, Juhi S Shah and 12 more

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

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Clinicogenomic Landscape and Function ofJCO precision oncology · 2026
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  7. Review
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  11. Review
  12. Article
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  14. Review
  15. Genetic Heterogeneity and Tissue-specific Patterns of Tumors with Multiple PIK3CA Mutations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Clinical Medicine Insights. Oncology · 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

22 authors at 6 institutions in 2 countries.

Yeji AnProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Jessica R AdamsProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada.
Daniel P HollernLineberger Comprehensive Cancer Center, Departments of Genetics and Pathology, University of North Carolina, Chapel Hill, NC 27599, USA.
Anthony ZhaoProgram in Developmental and Stem Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Stephen G ChangProgram in Developmental and Stem Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Miki S GamsProgram in Developmental and Stem Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Philip E D ChungDivision of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, and Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Xiaping HeLineberger Comprehensive Cancer Center, Departments of Genetics and Pathology, University of North Carolina, Chapel Hill, NC 27599, USA.
Rhea JangraProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada.
Juhi S ShahProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada.
Joanna YangProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada.
Lauren A BeckProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada.
Nandini RaghuramProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Katelyn J KozmaProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Amanda J LochProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada.
Wei WangProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada.
Cheng FanLineberger Comprehensive Cancer Center, Departments of Genetics and Pathology, University of North Carolina, Chapel Hill, NC 27599, USA.
Susan J DoneDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; The Campbell Family Institute for Breast Cancer Research at the Princess Margaret Cancer Centre and The Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
Eldad ZacksenhausDivision of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, and Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Cynthia J GuidosProgram in Developmental and Stem Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Charles M PerouLineberger Comprehensive Cancer Center, Departments of Genetics and Pathology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: cperou@med.unc.edu.
Sean E EganProgram in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G-0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. Electronic address: segan@sickkids.ca.
Hospital for Sick Children · CAUNC Lineberger Comprehensive Cancer CenterUniversity Health Network · CAUniversity of Toronto · CAPrincess Margaret Cancer Centre · CAUniversity of North Carolina at Chapel Hill · US

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3M
Therapeutic Targeting of Breast Cancer Tumor Initiating CellsR01CA148761 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEROU, CHARLES M, ROSEN, JEFFREY MARK · 2010 to 2025
$6.5M
Credentialing Mouse Models for Immune System Therapy ResearchR01CA195740 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEROU, CHARLES M, WONG, KWOK KIN · 2015 to 2017
$1.8M
Mouse Models of Metastatic Triple-Negative Breast Cancer for Therapeutic TestingR01CA195754 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEROU, CHARLES M, ROSEN, JEFFREY MARK · 2015 to 2017
$1.7M
Identifying Effective Immune Checkpoint Therapy Strategies in Triple Negative Breast CancerF32CA210427 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HOLLERN, DANIEL PATRICK · 2016 to 2018
$171k
NCI NIH HHS F32 CA210427NCI NIH HHS R01 CA148761NCI NIH HHS R01 CA195740NCI NIH HHS R01 CA195754NIEHS NIH HHS P30 ES010126
6 · The paper itself

Abstract

CDH1 and PIK3CA are the two most frequently mutated genes in invasive lobular carcinoma (ILC) of the breast. Transcription profiling has identified molecular subtypes for ILC, one of which, immune-related (IR), is associated with gene expression linked to lymphocyte and macrophage infiltration. Here, we report that deletion of Cdh1, together with activation of Pik3ca in mammary epithelium of genetically modified mice, leads to formation of IR-ILC-like tumors with immune cell infiltration, as well as gene expression linked to T-regulatory (Treg) cell signaling and activation of targetable immune checkpoint pathways. Interestingly, these tumors show enhanced Rac1- and Yap-dependent transcription and signaling, as well as sensitivity to PI3K, Rac1, and Yap inhibitors in culture. Finally, high-dimensional immunophenotyping in control mouse mammary gland and IR-ILC tumors by mass cytometry shows dramatic alterations in myeloid and lymphoid populations associated with immune suppression and exhaustion, highlighting the potential for therapeutic intervention via immune checkpoint regulators.

Indexed as

Gene Expression Regulation, NeoplasticMutationAdaptor Proteins, Signal TransducingAnimalsCadherinsCarcinoma, LobularCell Cycle ProteinsClass I Phosphatidylinositol 3-KinasesFemaleMammary Neoplasms, AnimalMiceMice, KnockoutMyeloid CellsNeoplasm InvasivenessPhosphatidylinositol 3-Kinasesrac GTP-Binding ProteinsAdaptor Proteins, Signal TransducingCadherinsCdh1 protein, mouseCell Cycle ProteinsClass I Phosphatidylinositol 3-KinasesPhosphatidylinositol 3-KinasesPik3ca protein, mouserac GTP-Binding ProteinsYap1 protein, mouseYAP-Signaling ProteinsCdh1Hif1aimmune checkpointimmune infiltrationlobular breast cancerPik3caRac1tumor-associated macrophagestumor-infiltrative lymphocytesYap

Identifiers

PMID30332649
PMCPMC6276789
OpenAlexW2896479296

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.