Evidence map›Paper›PMID 27375021›Full record

ArticleOncogene2017

Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy.

M Gugnoni, V Sancisi, G Gandolfi, G Manzotti, M Ragazzi, D Giordano, I Tamagnini, M Tigano, A Frasoldati, S Piana and 1 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 1 pooled it
10.1field-weighted citation impact, top 1% 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

127 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.

  1. Morphological and molecular characterization of epithelial ovarian cancer: SEOM-SEAP consensus guidelines for biomarker integration in clinical practice.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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67 more citing papers are in PubMed but not listed here.

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

11 authors at 1 institution in 1 country.

M GugnoniLaboratory of Translational Research, Department of Scientific Direction, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
V SancisiLaboratory of Translational Research, Department of Scientific Direction, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
G GandolfiLaboratory of Translational Research, Department of Scientific Direction, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
G ManzottiLaboratory of Translational Research, Department of Scientific Direction, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
M RagazziPathology Unit, Deptartment of Oncology and Advanced Technologies, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
D GiordanoOtolaryngology Unit, Department of General Surgery and Specialistic Unit, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
I TamagniniPathology Unit, Deptartment of Oncology and Advanced Technologies, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
M TiganoLaboratory of Translational Research, Department of Scientific Direction, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
A FrasoldatiEndocrinology Unit, Department of General Surgery and Specialistic Unit, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
S PianaPathology Unit, Deptartment of Oncology and Advanced Technologies, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
A CiarrocchiLaboratory of Translational Research, Department of Scientific Direction, Arcispedale S Maria Nuova-IRCCS, Reggio Emilia, Italy.
Istituti di Ricovero e Cura a Carattere Scientifico · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The transdifferentiation of epithelial cells toward a mesenchymal condition (EMT) is a complex process that allows tumor cells to migrate to ectopic sites. Cadherins are not just structural proteins, but they act as sensors of the surrounding microenvironment and as signaling centers for cellular pathways. However, the molecular mechanisms underlying these signaling functions remain poorly characterized. Cadherin-6 (CDH6) is a type 2 cadherin, which drives EMT during embryonic development and it is aberrantly re-activated in cancer. We recently showed that CDH6 is a TGFβ target and an EMT marker in thyroid cancer, suggesting a role for this protein in the progression of this type of tumor. Papillary thyroid carcinomas (PTCs) are usually indolent lesions. However, metastatic spreading occurs in about 5% of the cases. The identification of molecular markers that could early predict the metastatic potential of these lesions would be strategic to design more tailored approaches and reduce patients overtreatment. In this work, we assessed the role of CDH6 in the metastatic progression of thyroid cancer. We showed that loss of CDH6 expression profoundly changes cellular architecture, alters the inter-cellular interaction modalities and attenuates EMT features in thyroid cancer cells. Using a yeast two-hybrid screening approach, based on a thyroid cancer patients library, we showed that CDH6 directly interacts with GABARAP, BNIP3 and BNIP3L, and that through these interactions CDH6 restrains autophagy and promotes re-organization of mitochondrial network through a DRP1-mediated mechanism. Analysis of the LIR domains suggests that the interaction with the autophagic machinery may be a common feature of many cadherin family members. Finally, the analysis of CDH6 expression in a unique cohort of human PTCs showed that CDH6 expression marks specifically EMT cells. and it is strongly associated with metastatic behavior and worse outcome of PTCs.

Indexed as

AutophagyCadherinsCarcinomaCarcinoma, PapillaryEpithelial-Mesenchymal TransitionHumansNeoplasm MetastasisSignal TransductionThyroid Cancer, PapillaryThyroid NeoplasmsCadherins

Identifiers

PMID27375021
OpenAlexW2460632280

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.