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Cited by 238

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

RETRACTED: PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis

Samanta, Debangshu, Park, Youngrok, Andrabi, Shaida A., Shelton, Laura M., Gilkes, Daniele M., Semenza, Gregg L.·2016·Cancer Research

Abstract

Intratumoral hypoxia stimulates enrichment of breast cancer stem cells (BCSC), which are critical for metastasis and patient mortality. Here we report a metabolic adaptation that is required for hypoxia-induced BCSC enrichment and metastasis. Hypoxia-inducible factors coordinately regulate expression of genes encoding phosphoglycerate dehydrogenase (PHGDH) and five downstream enzymes in the serine synthesis pathway and mitochondrial one-carbon (folate) cycle. RNAi-mediated silencing of PHGDH expression in both estrogen receptor–positive and negative breast cancer cells led to decreased NADPH levels, disturbed mitochondrial redox homeostasis, and increased apoptosis, which abrogated BCSC enrichment under hypoxic conditions. PHGDH-deficient cells exhibited increased oxidant levels and apoptosis, as well as loss of BCSC enrichment, in response to treatment with carboplatin or doxorubicin. PHGDH-deficient cells were relatively weakly tumorigenic and tumors that did form were deficient in BCSCs, abolishing metastatic capacity. Our findings highlight a role for PHGDH in the formation of secondary (recurrent or metastatic) tumors, with potential implications for therapeutic targeting of advanced cancers. Cancer Res; 76(15); 4430–42. ©2016 AACR.

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Metadata

Authors
Samanta, D., Park, Y., Andrabi, S. A., Shelton, L. M., Gilkes, D. M., & Semenza, G. L.
Venue
Cancer Research
Published
2016-07-31
Volume
76
Issue
15
Pages
4430-4442
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2418570604
Cited by
238
References
19
FWCI
9.58
Type
journal article
Language
en
Status
Retracted
Open access
closed

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CoChat. (2026). Citation check: RETRACTED: PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis. https://app.cochat.ai/papers/10.1158/0008-5472.can-16-0530
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Samanta, D., Park, Y., Andrabi, S. A., Shelton, L. M., Gilkes, D. M., & Semenza, G. L. (2016). RETRACTED: PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis. Cancer Research. https://doi.org/10.1158/0008-5472.can-16-0530

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.