Evidence map›Paper›PMID 28614631›Full record

ArticleMolecular oncology2018

TRPM4 regulates Akt/GSK3-β activity and enhances β-catenin signaling and cell proliferation in prostate cancer cells.

Alfredo I Sagredo, Eduardo A Sagredo, Claudio Cappelli, Pablo Báez, Rodrigo E Andaur, Constanza Blanco, Julio C Tapia, César Echeverría, Oscar Cerda, Andrés Stutzin and 3 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% 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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
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  17. Monitoring trafficking and expression of hemagglutinin-tagged transient receptor potential melastatin 4 channel in mammalian cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023
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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

13 authors at 2 institutions in 1 country.

Alfredo I SagredoCentro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Eduardo A SagredoCentro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Claudio CappelliInstituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Pablo BáezDepartamento de Oncologia Basico-Clinica, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Rodrigo E AndaurDepartamento de Oncologia Basico-Clinica, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Constanza BlancoPrograma de Biología Celular y Molecular, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Julio C TapiaDepartamento de Oncologia Basico-Clinica, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
César EcheverríaCentro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Oscar CerdaPrograma de Biología Celular y Molecular, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Andrés StutzinInstituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Felipe SimonLaboratorio de Fisiopatologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
Katherine MarcelainCentro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Ricardo ArmisénCentro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
University of Chile · CLUniversidad Andrés Bello · CL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increased expression of the TRPM4 channel has been reported to be associated with the progression of prostate cancer. However, the molecular mechanism underlying its effect remains unknown. This work found that decreasing TRPM4 levels leads to the reduced proliferation of PC3 cells. This effect was associated with a decrease in total β-catenin protein levels and its nuclear localization, and a significant reduction in Tcf/Lef transcriptional activity. Moreover, TRPM4 silencing increases the Ser33/Ser37/Thr41 β-catenin phosphorylated population and reduces the phosphorylation of GSK-3β at Ser9, suggesting an increase in β-catenin degradation as the underlying mechanism. Conversely, TRPM4 overexpression in LNCaP cells increases the Ser9 inhibitory phosphorylation of GSK-3β and the total levels of β-catenin and its nonphosphorylated form. Finally, PC3 cells with reduced levels of TRPM4 showed a decrease in basal and stimulated phosphoactivation of Akt1, which is likely responsible for the decrease in GSK-3β activity in these cells. Our results also suggest that the effect of TRPM4 on Akt1 is probably mediated by an alteration in the calcium/calmodulin-EGFR axis, linking TRPM4 activity with the observed effects in β-catenin-related signaling pathways. These results suggest a role for TRPM4 channels in β-catenin oncogene signaling and underlying mechanisms, highlighting this ion channel as a new potential target for future therapies in prostate cancer.

Indexed as

beta CateninCalciumCalmodulinCell Line, TumorCell ProliferationDisease ProgressionGlycogen Synthase Kinase 3 betaHEK293 CellsHumansMalePC-3 CellsPhosphorylationProstatic NeoplasmsProto-Oncogene Proteins c-aktTRPM Cation ChannelsAKT1 protein, humanbeta CateninCalciumCalmodulinGlycogen Synthase Kinase 3 betaGSK3B protein, humanProto-Oncogene Proteins c-aktTRPM4 protein, humanTRPM Cation Channelsion channelprostate cancerTRPM4Wntβ-catenin

Identifiers

PMID28614631
PMCPMC5792731
OpenAlexW2762108088

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.