Evidence map›Paper›PMID 35437317›Full record

ArticleNature cancer2022

Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer.

Daniel P Bondeson, Brenton R Paolella, Adhana Asfaw, Michael V Rothberg, Thomas A Skipper, Carly Langan, Gabriel Mesa, Alfredo Gonzalez, Lauren E Surface, Kentaro Ito and 20 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
13.7field-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

45 citing papers in PubMed, 76 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. TGFβ signaling regulates the response of the skeleton to phosphate.bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. USP14-mediated metabolic competition impairs CD8+ T cell immunosurveillance in hepatocellular carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
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  20. Article
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

30 authors at 2 institutions in 1 country.

Daniel P Bondeson *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brenton R Paolella *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3394-828X
Adhana AsfawBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael V RothbergBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Thomas A SkipperBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Carly LanganBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Gabriel MesaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Alfredo GonzalezBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Lauren E SurfaceEndocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Kentaro ItoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Mariya KazachkovaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
William N ColganBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8328-4672
Allison WarrenBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Joshua M DempsterBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3634-9576
John M Krill-BurgerBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9614-4671
Maria EricssonHarvard Medical School, Boston, MA, USA.
Andrew A TangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Iris FungBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Emily S ChambersBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Mai AbdusamadBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nancy DumontBroad Institute of MIT and Harvard, Cambridge, MA, USA.
John G DoenchBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3707-9889
Federica PiccioniBroad Institute of MIT and Harvard, Cambridge, MA, USA.
David E RootBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5122-861X
Jesse BoehmBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6795-6336
William C HahnBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2840-9791
Michael MannstadtEndocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
James M McFarlandBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9978-480X
Francisca VazquezBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2857-4685
Todd R GolubBroad Institute of MIT and Harvard, Cambridge, MA, USA. golub@broadinstitute.org.ORCID http://orcid.org/0000-0003-0113-2403
Broad Institute · USHarvard University · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Making cancer precision medicine real: bottlenecks and opportunitiesR35CA242457 · NCI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2019 to 2025
$6.9M
Investigating degradation as a therapeutic strategy against the Pseudo-kinase KSRK00CA212229 · NCI · BROAD INSTITUTE, INC. · PI BONDESON, DANIEL · 2018 to 2021
$363k
Investigating degradation as a therapeutic strategy against the Pseudo-kinase KSRF99CA212229 · NCI · YALE UNIVERSITY · PI BONDESON, DANIEL · 2016 to 2017
$89k
NCI NIH HHS F99 CA212229NCI NIH HHS K00 CA212229NCI NIH HHS P30 CA006516NCI NIH HHS R35 CA242457
6 · The paper itself

Abstract

Despite advances in precision medicine, the clinical prospects for patients with ovarian and uterine cancers have not substantially improved. Here, we analyzed genome-scale CRISPR-Cas9 loss-of-function screens across 851 human cancer cell lines and found that frequent overexpression of SLC34A2-encoding a phosphate importer-is correlated with sensitivity to loss of the phosphate exporter XPR1, both in vitro and in vivo. In patient-derived tumor samples, we observed frequent PAX8-dependent overexpression of SLC34A2, XPR1 copy number amplifications and XPR1 messenger RNA overexpression. Mechanistically, in SLC34A2-high cancer cell lines, genetic or pharmacologic inhibition of XPR1-dependent phosphate efflux leads to the toxic accumulation of intracellular phosphate. Finally, we show that XPR1 requires the novel partner protein KIDINS220 for proper cellular localization and activity, and that disruption of this protein complex results in acidic "vacuolar" structures preceding cell death. These data point to the XPR1-KIDINS220 complex and phosphate dysregulation as a therapeutic vulnerability in ovarian cancer.

Indexed as

Membrane ProteinsNerve Tissue ProteinsOvarian NeoplasmsFemaleHumansPhosphatesReceptors, G-Protein-CoupledReceptors, VirusXenotropic and Polytropic Retrovirus ReceptorKIDINS220 protein, humanMembrane ProteinsNerve Tissue ProteinsPhosphatesReceptors, G-Protein-CoupledReceptors, VirusXenotropic and Polytropic Retrovirus ReceptorXPR1 protein, human

Identifiers

PMID35437317
PMCPMC9246846
OpenAlexW4225977695

What OpenQuestion holds

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Registered trials

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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.