Evidence map›Paper›PMID 25852060›Full record

ArticleMolecular cancer therapeutics2015

Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101.

Sahra Borges, Edith A Perez, E Aubrey Thompson, Derek C Radisky, Xochiquetzal J Geiger, Peter Storz

Open access · greenAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

47 citing papers in PubMed, 74 citations in OpenAlex.

  1. Mechanical forces stimulate Golgi export.The Journal of cell biology · 2026
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  3. Golgi Drivers of Cancer.Sub-cellular biochemistry · 2026
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  9. Protein kinase D1 - A targetable mediator of pancreatic cancer development.Biochimica et biophysica acta. Molecular cell research · 2024
    Review
  10. Article
  11. Article
  12. Potential role for protein kinase D inhibitors in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2023
    Review
  13. Loss of Protein Kinase D2 Activity Protects Against Bleomycin-Induced Dermal Fibrosis in Mice.Laboratory investigation; a journal of technical methods and pathology · 2023
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Effect of protein kinase D inhibitor CRT0066101 on the cell migration of salivary adenoid cystic carcinoma.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2022
    Article
  19. Article
  20. Review
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

6 authors at 1 institution in 1 country.

Sahra BorgesDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
Edith A PerezDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida. Department of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida.
E Aubrey ThompsonDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
Derek C RadiskyDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
Xochiquetzal J GeigerLaboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida.
Peter StorzDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida. storz.peter@mayo.edu.
Jacksonville College · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Protein Kinase D in oncogenic oxidative stress signalingR01CA140182 · NCI · MAYO CLINIC JACKSONVILLE · PI STORZ, PETER · 2010 to 2014
$1.5M
Role of Protein Kinase D in Actin Remodeling and Cell MotiliyR01GM086435 · NIGMS · MAYO CLINIC JACKSONVILLE · PI STORZ, PETER · 2010 to 2013
$1.1M
NCI NIH HHS CA116201NCI NIH HHS CA140182NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA140182NIGMS NIH HHS GM086435NIGMS NIH HHS R01 GM086435
6 · The paper itself

Abstract

Invasive ductal carcinomas (IDC) of the breast are associated with altered expression of hormone receptors (HR), amplification or overexpression of HER2, or a triple-negative phenotype. The most aggressive cases of IDC are characterized by a high proliferation rate, a great propensity to metastasize, and their ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted therapy. Using progression tissue microarrays, we here demonstrate that the serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in estrogen receptor (ER)-negative (ER(-)) tumors. We identify direct binding of the ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression. Loss of ER results in upregulation of PKD3, leading to all hallmarks of aggressive IDC, including increased cell proliferation, migration, and invasion. This identifies ER(-) breast cancers as ideal for treatment with the PKD inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with this inhibitor targets all tumorigenic processes in vitro and decreases growth of primary tumors and metastasis in vivo. Our data strongly support the development of PKD inhibitors for clinical use for ER(-) breast cancers, including the triple-negative phenotype.

Indexed as

AnimalsBlotting, WesternBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationFemaleHumansImmunohistochemistryLung NeoplasmsLymphatic MetastasisMCF-7 CellsMice, Inbred NODMice, SCIDMicroscopy, ConfocalNeoplasm InvasivenessCRT 0066101Protein Kinase Cprotein kinase C nuProtein Kinase InhibitorsPyrimidinesReceptors, Estrogen

Identifiers

PMID25852060
PMCPMC4458391
OpenAlexW2142422106

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.