Evidence map›Paper›PMID 28239645›Full record

ArticleJCI insight2017

PML promotes metastasis of triple-negative breast cancer through transcriptional regulation of HIF1A target genes.

Manfredi Ponente, Letizia Campanini, Roberto Cuttano, Andrea Piunti, Giacomo A Delledonne, Nadia Coltella, Roberta Valsecchi, Alessandra Villa, Ugo Cavallaro, Linda Pattini and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 68 citations in OpenAlex.

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  20. Metabolism and immunity in breast cancer.Frontiers of medicine · 2021
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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

12 authors at 4 institutions in 1 country.

Manfredi PonenteDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Letizia CampaniniDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Roberto CuttanoDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Andrea PiuntiDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Giacomo A DelledonneDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Nadia ColtellaDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Roberta ValsecchiDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Alessandra VillaDepartment of Experimental Oncology and Molecular Medicine Program, European Institute of Oncology, Milan, Italy.
Ugo CavallaroDepartment of Experimental Oncology and Molecular Medicine Program, European Institute of Oncology, Milan, Italy.
Linda PattiniDepartment of Electronics, Information and Bioengineering, Politecnico di Milano, Italy.
Claudio DoglioniDepartment of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Rosa BernardiDivision of Experimental Oncology, IRCCS San Raffaele Scientific Institute.
Istituti di Ricovero e Cura a Carattere Scientifico · ITIstituto di Ricovero e Cura a Carattere Scientifico San RaffaeleVita-Salute San Raffaele University · ITPolitecnico di Milano · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Elucidating the molecular basis of tumor metastasis is pivotal for eradicating cancer-related mortality. Triple-negative breast cancer (TNBC) encompasses a class of aggressive tumors characterized by high rates of recurrence and metastasis, as well as poor overall survival. Here, we find that the promyelocytic leukemia protein PML exerts a prometastatic function in TNBC that can be targeted by arsenic trioxide. We found that, in TNBC patients, constitutive HIF1A activity induces high expression of PML, along with a number of HIF1A target genes that promote metastasis at multiple levels. Intriguingly, PML controls the expression of these genes by binding to their regulatory regions along with HIF1A. This mechanism is specific to TNBC cells and does not occur in other subtypes of breast cancer where PML and prometastatic HIF1A target genes are underexpressed. As a consequence, PML promotes cell migration, invasion, and metastasis in TNBC cell and mouse models. Notably, pharmacological inhibition of PML with arsenic trioxide, a PML-degrading agent used to treat promyelocytic leukemia patients, delays tumor growth, impairs TNBC metastasis, and cooperates with chemotherapy by preventing metastatic dissemination. In conclusion, we report identification of a prometastatic pathway in TNBC and suggest clinical development toward the use of arsenic trioxide for TNBC patients.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsCell Line, TumorCell MovementHEK293 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitMCF-7 CellsMiceMice, Inbred NODMice, SCIDNeoplasm InvasivenessNeoplasm MetastasisNeoplasm TransplantationNIH 3T3 CellsPromyelocytic Leukemia ProteinHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitPML protein, humanPromyelocytic Leukemia Protein

Identifiers

PMID28239645
PMCPMC5313064
OpenAlexW2588604855

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.