Evidence map›Paper›PMID 30477496›Full record

ArticleBMC veterinary research2018

An evaluation of TAZ and YAP crosstalk with TGFβ signalling in canine osteosarcoma suggests involvement of hippo signalling in disease progression.

Anita K Luu, Courtney R Schott, Robert Jones, Andrew C Poon, Brandon Golding, Roa'a Hamed, Benjamin Deheshi, Anthony Mutsaers, Geoffrey A Wood, Alicia M Viloria-Petit

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

Article in BMC veterinary research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
1.8field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Molecular Mechanisms of Canine Osteosarcoma Metastasis.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Review
  9. Review
  10. 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

10 authors at 1 institution in 1 country.

Anita K LuuDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Courtney R SchottDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Robert JonesDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Andrew C PoonDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Brandon GoldingDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Roa'a HamedDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Benjamin DeheshiMedical City Forth Worth, HCA affiliated Hospital, 900 8th Ave, Fort Worth, TX, 76104, USA.
Anthony MutsaersDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Geoffrey A WoodDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada. gewood@uoguelph.ca.
Alicia M Viloria-PetitDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada. aviloria@uoguelph.ca.
University of Guelph · CA

Funding

OVC Pet Trust 050411OVC Pet Trust 052655
6 · The paper itself

Abstract

backgroundOsteosarcoma (OSA) is the most common bone cancer in canines. Both transforming growth factor beta (TGFβ) and Hippo pathway mediators have important roles in bone development, stemness, and cancer progression. The role of Hippo signalling effectors TAZ and YAP has never been addressed in canine OSA. Further, the cooperative role of TGFβ and Hippo signalling has yet to be explored in osteosarcoma. To address these gaps, this study investigated the prognostic value of TAZ and YAP alone and in combination with pSmad2 (a marker of active TGFβ signalling), as well as the involvement of a TGFβ-Hippo signalling crosstalk in tumourigenic properties of OSA cells in vitro. An in-house trial tissue microarray (TMA) which contained 16 canine appendicular OSA cases undergoing standard care and accompanying follow-up was used to explore the prognostic role of TAZ, YAP and pSmad2. Published datasets were used to test associations between TAZ and YAP mRNA levels, metastasis, and disease recurrence. Small interfering RNAs specific to TAZ and YAP were utilized in vitro alone or in combination with TGFβ treatment to determine their role in OSA viability, proliferation and migration.

resultsPatients with low levels of both YAP and pSmad2 when evaluated in combination had a significantly longer time to metastasis (log-rank test, p = 0.0058) and a longer overall survival (log rank test, p = 0.0002). No similar associations were found for TAZ and YAP mRNA levels. In vitro, TAZ knockdown significantly decreased cell viability, proliferation, and migration in metastatic cell lines, while YAP knockdown significantly decreased viability in three cell lines, and migration in two cell lines, derived from either primary tumours or their metastases. The impact of TGFβ signaling activation on these effects was cell line-dependent.

conclusionsYAP and pSmad2 have potential prognostic value in canine appendicular osteosarcoma. Inhibiting YAP and TAZ function could lead to a decrease in viability, proliferation, and migratory capacity of canine OSA cells. Assessment of YAP and pSmad2 in larger patient cohorts in future studies are needed to further elucidate the role of TGFβ-Hippo signalling crosstalk in canine OSA progression.

Indexed as

Signal TransductionAnimalsBone NeoplasmsCell Line, TumorDisease ProgressionDog DiseasesDogsFemaleMaleOsteosarcomaSmad2 ProteinTranscription FactorsTransforming Growth Factor betaSmad2 ProteinTranscription FactorsTransforming Growth Factor betaCanine osteosarcomaHippo signallingMetastasisPrognostic markerTAZTGFβWWTR1YAP1

Identifiers

PMID30477496
PMCPMC6258471
OpenAlexW2902481648

What Socratic 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 Socratic graph.