↓ Skip to main content

NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins

Overview of attention for article published in Cancer Discovery, June 2022
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

Mentioned by

twitter
49 tweeters
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins
Published in
Cancer Discovery, June 2022
DOI 10.1158/2159-8290.cd-22-0043
Pubmed ID
Authors

Santana-Codina, Naiara, Quiles del Rey, Maria, Kapner, Kevin S., Zhang, Huan, Gikandi, Ajami, Malcolm, Callum, Poupault, Clara, Kuljanin, Miljan, John, Kristen M., Biancur, Douglas E., Chen, Brandon, Das, Nupur K., Lowder, Kristen E., Hennessey, Connor J., Huang, Wesley, Yang, Annan, Shah, Yatrik M., Nowak, Jonathan A., Aguirre, Andrew J., Mancias, Joseph D.

Abstract

Pancreatic ductal adenocarcinomas (PDAC) depend on autophagy for survival; however, the metabolic substrates that autophagy provides to drive PDAC progression are unclear. Ferritin, the cellular iron storage complex, is targeted for lysosomal degradation (ferritinophagy) by the selective autophagy adaptor NCOA4, resulting in release of iron for cellular utilization. Using patient-derived and murine models of PDAC we now demonstrate that ferritinophagy is upregulated in PDAC to sustain iron availability thereby promoting tumor progression. Quantitative proteomics reveals that ferritinophagy fuels iron-sulfur cluster protein synthesis to support mitochondrial homeostasis. Targeting NCOA4 leads to tumor growth delay and prolonged survival but with development of compensatory iron acquisition pathways. Finally, enhanced ferritinophagy accelerates PDAC tumorigenesis, and an elevated ferritinophagy expression signature predicts for poor prognosis in PDAC patients. Together, our data reveal that maintenance of iron homeostasis is a critical function of PDAC autophagy, and we define NCOA4-mediated ferritinophagy as a therapeutic target in PDAC.

Twitter Demographics

The data shown below were collected from the profiles of 49 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Attention Score in Context

This research output has an Altmetric Attention Score of 29. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 July 2022.
All research outputs
#1,072,598
of 21,749,791 outputs
Outputs from Cancer Discovery
#515
of 3,485 outputs
Outputs of similar age
#19,558
of 302,894 outputs
Outputs of similar age from Cancer Discovery
#21
of 131 outputs
Altmetric has tracked 21,749,791 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,485 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.6. This one has done well, scoring higher than 85% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 302,894 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 131 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.