Evidence map›Paper›PMID 27663795›Full record

ArticleBreast cancer research : BCR2016

PRKCQ promotes oncogenic growth and anoikis resistance of a subset of triple-negative breast cancer cells.

Jessica Byerly, Gwyneth Halstead-Nussloch, Koichi Ito, Igor Katsyv, Hanna Y Irie

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
0.5field-weighted citation impact, top 28% 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

31 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

5 authors at 2 institutions in 1 country.

Jessica ByerlyDivision of Hematology and Medical Oncology, Department of Medicine and Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, USA.
Gwyneth Halstead-NusslochDivision of Hematology and Medical Oncology, Department of Medicine and Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, USA.
Koichi ItoDivision of Hematology and Medical Oncology, Department of Medicine and Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, USA.
Igor KatsyvDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Hanna Y IrieDivision of Hematology and Medical Oncology, Department of Medicine and Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, USA. Hanna.Irie@mssm.edu.ORCID 0000-0001-5288-7318
Icahn School of Medicine at Mount Sinai · USTisch Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe protein kinase C (PKC) family comprises distinct classes of proteins, many of which are implicated in diverse cellular functions. Protein tyrosine kinase C theta isoform (PRKCQ)/PKCθ, a member of the novel PKC family, may have a distinct isoform-specific role in breast cancer. PKCθ is preferentially expressed in triple-negative breast cancer (TNBC) compared to other breast tumor subtypes. We hypothesized that PRKCQ/PKCθ critically regulates growth and survival of a subset of TNBC cells.

methodsTo elucidate the role of PRKCQ/PKCθ in regulating growth and anoikis resistance, we used both gain and loss of function to modulate expression of PRKCQ. We enhanced expression of PKCθ (kinase-active or inactive) in non-transformed breast epithelial cells (MCF-10A) and assessed effects on epidermal growth factor (EGF)-independent growth, anoikis, and migration. We downregulated expression of PKCθ in TNBC cells, and determined effects on in vitro and in vivo growth and survival. TNBC cells were also treated with a small molecule inhibitor to assess requirement for PKCθ kinase activity in the growth of TNBC cells.

resultsPRKCQ/PKCθ can promote oncogenic phenotypes when expressed in non-transformed MCF-10A mammary epithelial cells; PRKCQ/PKCθ enhances anchorage-independent survival, growth-factor-independent proliferation, and migration. PKCθ expression promotes retinoblastoma (Rb) phosphorylation and cell-cycle progression under growth factor-deprived conditions that typically induce cell-cycle arrest of MCF-10A breast epithelial cells. Proliferation and Rb phosphorylation are dependent on PKCθ-stimulated extracellular signal-related kinase (Erk)/mitogen-activated protein kinase (MAPK) activity. Enhanced Erk/MAPK activity is dependent on the kinase activity of PKCθ, as overexpression of kinase-inactive PKCθ does not stimulate Erk/MAPK or Rb phosphorylation or promote growth-factor-independent proliferation. Downregulation of PRKCQ/PKCθ in TNBC cells enhances anoikis, inhibits growth in 3-D Matrigel

conclusionsEnhanced PRKCQ/PKCθ expression can promote growth-factor-independent growth, anoikis resistance, and migration. PRKCQ critically regulates growth and survival of a subset of TNBC. Inhibition of PKCθ kinase activity may be an attractive therapeutic approach for TNBC, a subtype in need of improved targeted therapies.

Indexed as

AnoikisAnimalsCell CycleCell Line, TumorCell MovementCell ProliferationDisease Models, AnimalEpidermal Growth FactorFemaleGene ExpressionHeterograftsHumansIsoenzymesMAP Kinase Signaling SystemPhosphorylationProtein Kinase CEpidermal Growth FactorIsoenzymesPRKCQ protein, humanProtein Kinase CProtein Kinase C-thetaRetinoblastoma ProteinAnoikisEGF-independent growthPRKCQ/PKCθTriple-negative breast cancer

Identifiers

PMID27663795
PMCPMC5034539
OpenAlexW2522978034

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.