Evidence map›Paper›PMID 33238381›Full record

ArticleCells2020

LIMD2 Regulates Key Steps of Metastasis Cascade in Papillary Thyroid Cancer Cells via MAPK Crosstalk.

Rodrigo Pinheiro Araldi, Thatiana Correa de Melo, Débora Levy, Dener Madeiro de Souza, Beatriz Maurício, Gabriel Avelar Colozza-Gama, Sergio Paulo Bydlowski, Hongzhuang Peng, Frank J Rauscher, Janete Maria Cerutti

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. 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 5 institutions in 2 countries.

Rodrigo Pinheiro AraldiGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo/EPM, São Paulo, SP 04039-032, Brazil.ORCID 0000-0001-8288-2577
Thatiana Correa de MeloPrograma de Pós-graduação em Biociências, Universidade Federal da Integração Latino-Americana (UNILA), Foz do Iguaçu, PR 85866-000, Brazil.
Débora LevyLaboratory of Histocompatibility and Cellular Immunity, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP 05404-000, Brazil.ORCID 0000-0001-7492-997X
Dener Madeiro de SouzaGenetics Laboratory, Instituto Butantan, São Paulo, SP 05503-900, Brazil.
Beatriz MaurícioLaboratory of Cell Biology, Instituto Butantan, São Paulo, SP 05503-900, Brazil.
Gabriel Avelar Colozza-GamaGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo/EPM, São Paulo, SP 04039-032, Brazil.
Sergio Paulo BydlowskiLaboratory of Histocompatibility and Cellular Immunity, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP 05404-000, Brazil.ORCID 0000-0002-7582-5942
Hongzhuang PengThe Wistar Institute, Philadelphia, PA 19104, USA.
Frank J RauscherThe Wistar Institute, Philadelphia, PA 19104, USA.
Janete Maria CeruttiGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo/EPM, São Paulo, SP 04039-032, Brazil.
Universidade Federal de São Paulo · BRInstituto Butantan · BRThe Wistar Institute · USUniversidade de São Paulo · BRUniversidade Federal da Integração Latino-Americana · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although papillary thyroid carcinoma (PTC) has a good prognosis, 20-90% of patients show metastasis to regional lymph nodes and 10-15% of patients show metastasis to distant sites. Metastatic disease represents the main clinical challenge that impacts survival rate. We previously showed that LIMD2 was a novel metastasis-associated gene. In this study, to interrogate the role of LIMD2 in cancer invasion and metastasis, we used CRISPR-mediated knockout (KO) of LIMD2 in PTC cells (BCPAP and TPC1). Western blot and high-content screening (HCS) analysis confirmed functional KO of LIMD2. LIMD2 KO reduced in vitro invasion and migration. Ultrastructural analyses showed that cell polarity and mitochondria function and morphology were restored in LIMD2 KO cells. To unveil the signals supervising these phenotypic changes, we employed phospho-protein array. Several members of the MAPK superfamily showed robust reduction in phosphorylation. A Venn diagram displayed the overlap of kinases with reduced phosphorylation in both cell lines and showed that they were able to initiate or sustain the epithelial-mesenchymal transition (EMT) and DNA damage checkpoint. Flow cytometry and HCS validation analyses further corroborated the phospho-protein array data. Collectively, our findings show that LIMD2 enhances phosphorylation of kinases associated with EMT and invasion. Through cooperation with different kinases, it contributes to the increased genomic instability that ultimately promotes PTC progression.

Indexed as

Cell Line, TumorEpithelial-Mesenchymal TransitionFemaleHumansMaleMitogen-Activated Protein Kinase KinasesNeoplasm MetastasisNeoplasm ProteinsThyroid Cancer, PapillaryLIMD2 protein, humanMitogen-Activated Protein Kinase KinasesNeoplasm ProteinsBRAF V600ECRISPR/Cas9epithelial-to-mesenchymal transitionLIMD2papillary thyroid carcinoma

Identifiers

PMID33238381
PMCPMC7700534
OpenAlexW3109983536

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.