Evidence map›Paper›PMID 35435804›Full record

ArticleAutophagy2023

Impaired degradation of YAP1 and IL6ST by chaperone-mediated autophagy promotes proliferation and migration of normal and hepatocellular carcinoma cells.

Enrico Desideri, Serena Castelli, Coralie Dorard, Stefanie Toifl, Gian Luca Grazi, Maria Rosa Ciriolo, Manuela Baccarini

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
5.3field-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

41 citing papers in PubMed, 49 citations in OpenAlex.

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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

7 authors at 4 institutions in 3 countries.

Enrico DesideriDepartment of Biology, University of Rome "Tor Vergata", Rome, Italy.
Serena CastelliDepartment of Biology, University of Rome "Tor Vergata", Rome, Italy.
Coralie DorardDepartment of Microbiology, Immunology and Genetics; Center of Molecular Biology, University of Vienna; Max Perutz Labs, Vienna, Austria.
Stefanie ToiflDepartment of Microbiology, Immunology and Genetics; Center of Molecular Biology, University of Vienna; Max Perutz Labs, Vienna, Austria.
Gian Luca GraziSurgery Unit, Department of Clinical and Experimental Oncology, IRCCS - Regina Elena National Cancer InstituteHepato-Pancreato-Biliary, Rome, Italy.
Maria Rosa CirioloDepartment of Biology, University of Rome "Tor Vergata", Rome, Italy.
Manuela BaccariniDepartment of Microbiology, Immunology and Genetics; Center of Molecular Biology, University of Vienna; Max Perutz Labs, Vienna, Austria.
University of Rome Tor Vergata · ITUniversity of Vienna · ATIstituti di Ricovero e Cura a Carattere Scientifico · ITMax Perutz Labs · AT

Funding

Austrian Science Fund FWF P 28539Austrian Science Fund FWF W 1261
6 · The paper itself

Abstract

Impaired degradation of the transcriptional coactivator YAP1 and IL6ST (interleukin 6 cytokine family signal transducer), two proteins deregulated in liver cancer, has been shown to promote tumor growth. Here, we demonstrate that YAP1 and IL6ST are novel substrates of chaperone-mediated autophagy (CMA) in human hepatocellular carcinoma (HCC) and hepatocyte cell lines. Knockdown of the lysosomal CMA receptor LAMP2A increases protein levels of YAP1 and IL6ST, without changes in mRNA expression. Additionally, both proteins show KFERQ-dependent binding to the CMA chaperone HSPA8 and accumulate into isolated lysosomes after stimulation of CMA by prolonged starvation. We further show that LAMP2A downregulation promotes the proliferation and migration in HCC cells and a human hepatocyte cell line, and that it does so in a YAP1- and IL6ST-dependent manner. Finally, LAMP2A expression is downregulated, and YAP1 and IL6ST expression is upregulated, in human HCC biopsies. Taken together, our work reveals a novel mechanism that controls the turnover of two cancer-relevant proteins and suggests a tumor suppressor function of CMA in the liver, advocating for the exploitation of CMA activity for diagnostic and therapeutic purposes.

Indexed as

Carcinoma, HepatocellularChaperone-Mediated AutophagyLiver NeoplasmsAdaptor Proteins, Signal TransducingAutophagyCell LineCell ProliferationCytokine Receptor gp130HumansInterleukin-6Lysosomal-Associated Membrane Protein 2LysosomesAdaptor Proteins, Signal TransducingCytokine Receptor gp130IL6ST protein, humanInterleukin-6Lysosomal-Associated Membrane Protein 2Chaperone-mediated autophagyhepatocellular carcinomaIL6STKFERQ motifLAMP2Amigrationproliferationprotein degradationYAP1

Identifiers

PMID35435804
PMCPMC9809932
OpenAlexW4224121378

What OpenQuestion holds

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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 OpenQuestion graph.