Evidence map›Paper›PMID 34244607›Full record

ArticleOncogene2021

PAX8 plays an essential antiapoptotic role in uterine serous papillary cancer.

Basem Fares, Liron Berger, Einav Bangiev-Girsh, Reli Rachel Kakun, Dima Ghannam-Shahbari, Yuval Tabach, Yaniv Zohar, Eyal Gottlieb, Ruth Perets

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Single-nuclei sequencing of uterine serous carcinoma reveals racial differences in immune signaling.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. Article
  5. Article
  6. PAX8 in the Junction between Development and Tumorigenesis.International journal of molecular sciences · 2022
    Review
  7. 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

9 authors at 3 institutions in 1 country.

Basem FaresThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Liron BergerDivision of Oncology, The Clinical Research Institute at Rambam (CRIR), Rambam Health Care Campus, Haifa, Israel.
Einav Bangiev-GirshThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Reli Rachel KakunThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Dima Ghannam-ShahbariThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Yuval TabachDepartment of Developmental Biology & Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID http://orcid.org/0000-0001-9521-3217
Yaniv ZoharDepartment of Pathology, Rambam Health Care Campus, Technion-Israel Institute of Technology, Haifa, Israel.
Eyal GottliebThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.ORCID http://orcid.org/0000-0002-9770-0956
Ruth PeretsThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Ru_Perets@RMC.gov.il.ORCID http://orcid.org/0000-0001-7216-6577
Technion – Israel Institute of Technology · ILRambam Health Care Campus · ILHebrew University of Jerusalem · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Endometrial carcinoma (EC) is the fourth-most common cancer in women in the United States, and generally carries a favorable prognosis. However, about 10% of EC patients have a rare and aggressive form, uterine serous papillary carcinoma (USPC), which carries a much higher mortality rate. The developmental transcription factor PAX8 is expressed in nearly 100% of USPCs. We show that PAX8 plays a critical antiapoptotic role in USPC and this role is established via transcriptional activation of two aberrant signaling pathways. First, PAX8 positively regulates mutated p53, and missense p53 mutations have an oncogenic gain of function effect. Second, PAX8 directly transcriptionally regulates p21, in a p53-independent manner, and p21 acquires a growth promoting role that is mediated via cytoplasmic localization of the protein. We propose that mutated p53 and cytoplasmic p21 can independently mediate the pro-proliferative role of PAX8 in USPC. In addition, we performed a genome-wide transcriptome analysis to detect pathways that are regulated by PAX8, and propose that metabolism and HIF-1alpha -related pathways are potential candidates for mediating the role of PAX8 in USPC. Taken together our findings demonstrate for the first time that PAX8 is an essential lineage marker in USPC, and suggest its mechanism of action.

Indexed as

ApoptosisPAX8 Transcription FactorTumor Suppressor Protein p53Uterine NeoplasmsCarcinoma, PapillaryCell Line, TumorCyclin-Dependent Kinase Inhibitor p21Cystadenocarcinoma, SerousFemaleGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitPaired Box Transcription FactorsSignal TransductionCyclin-Dependent Kinase Inhibitor p21Hypoxia-Inducible Factor 1, alpha SubunitPaired Box Transcription FactorsPAX8 protein, humanPAX8 Transcription FactorTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID34244607
OpenAlexW3177806111

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.