Evidence map›Paper›PMID 26839364›Full record

ArticleDevelopment (Cambridge, England)2016

Mammary epithelial tubes elongate through MAPK-dependent coordination of cell migration.

Robert J Huebner, Neil M Neumann, Andrew J Ewald

Open access · greenAbstract read
In one paragraph

Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.6field-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

44 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Mechanical coupling of supracellular stress amplification and tissue fluidization during exit from quiescence.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Collective behaviours in organoids.Current opinion in cell biology · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. The Cellular Organization of the Mammary Gland: Insights From Microscopy.Journal of mammary gland biology and neoplasia · 2021
    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

3 authors at 2 institutions in 1 country.

Robert J HuebnerDepartments of Cell Biology, Oncology, and Biomedical Engineering, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, 452 Rangos Building, Baltimore, MD 21205, USA.
Neil M NeumannDepartments of Cell Biology, Oncology, and Biomedical Engineering, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, 452 Rangos Building, Baltimore, MD 21205, USA.
Andrew J EwaldDepartments of Cell Biology, Oncology, and Biomedical Engineering, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, 452 Rangos Building, Baltimore, MD 21205, USA andrew.ewald@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
NCI NIH HHS NCI P30 CA006973NCI NIH HHS P30 CA006973NIGMS NIH HHS T32 GM007309NIGMS NIH HHS T32 GM007445PHS HHS NIGMS 2T32GM007445PHS HHS NIGMS 3T32GM007309
6 · The paper itself

Abstract

Mammary branching morphogenesis is regulated by receptor tyrosine kinases (RTKs). We sought to determine how these RTK signals alter proliferation and migration to accomplish tube elongation in mouse. Both behaviors occur but it has been difficult to determine their relative contribution to elongation in vivo, as mammary adipocytes scatter light and limit the depth of optical imaging. Accordingly, we utilized 3D culture to study elongation in an experimentally accessible setting. We first used antibodies to localize RTK signals and discovered that phosphorylated ERK1/2 (pERK) was spatially enriched in cells near the front of elongating ducts, whereas phosphorylated AKT was ubiquitous. We next observed a gradient of cell migration speeds from rear to front of elongating ducts, with the front characterized by both high pERK and the fastest cells. Furthermore, cells within elongating ducts oriented both their protrusions and their migration in the direction of tube elongation. By contrast, cells within the organoid body were isotropically protrusive. We next tested the requirement for proliferation and migration. Early inhibition of proliferation blocked the creation of migratory cells, whereas late inhibition of proliferation did not block continued duct elongation. By contrast, pharmacological inhibition of either MEK or Rac1 signaling acutely blocked both cell migration and duct elongation. Finally, conditional induction of MEK activity was sufficient to induce collective cell migration and ductal elongation. Our data suggest a model for ductal elongation in which RTK-dependent proliferation creates motile cells with high pERK, the collective migration of which acutely requires both MEK and Rac1 signaling.

Indexed as

Cell MovementAnimalsAnisotropyCell ProliferationEpithelial CellsExtracellular Signal-Regulated MAP KinasesFemaleHumansMammary Glands, AnimalMice, TransgenicMitogen-Activated Protein Kinase KinasesMorphogenesisOrganoidsPhosphorylationrac1 GTP-Binding ProteinSignal TransductionExtracellular Signal-Regulated MAP KinasesMitogen-Activated Protein Kinase Kinasesrac1 GTP-Binding ProteinBranching morphogenesisCollective cell migrationEpithelial developmentMammary glandMAPK signalingTubulogenesis

Identifiers

PMID26839364
PMCPMC4813284
OpenAlexW2304754051

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.