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Cited by 160

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation

Saito, Sakae, Furuno, Aki, Sakurai, Junko, Sakamoto, Asami, Park, Hae-Ryong, Shin-ya, Kazuo, Tsuruo, Takashi, Tomida, Akihiro·2009·Cancer Research

Abstract

Glucose deprivation, a cell condition that occurs in solid tumors, activates the unfolded protein response (UPR). A key feature of the UPR is the transcription program activation, which allows the cell to survive under stress conditions. Here, we show that the UPR transcription program is disrupted by the antidiabetic biguanides metformin, buformin, and phenformin depending on cellular glucose availability. These drugs inhibit production of the UPR transcription activators XBP1 and ATF4 and induce massive cell death during glucose deprivation as did the antitumor macrocyclic compound versipelostatin. Gene expression profiling shows remarkable similarity in the modes of action of biguanides and versipelostatin determined by the broad range of glucose deprivation-inducible genes. Importantly, during glucose deprivation, most of the biguanide suppression genes overlap with the genes induced by tunicamycin, a chemical UPR inducer. Gene expression profiling also identifies drug-driven signatures as a tool for discovering pharmacologic UPR modulators. Our findings show that disrupting the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical genomic basis for developing UPR-targeting drugs against solid tumors. [Cancer Res 2009;69(10):4225–34]

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Metadata

Authors
Saito, S., Furuno, A., Sakurai, J., Sakamoto, A., Park, H.-R., Shin-ya, K., Tsuruo, T., & Tomida, A.
Venue
Cancer Research
Published
2009-05-15
Volume
69
Issue
10
Pages
4225-4234
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2121173674
Cited by
160
References
11
FWCI
4.55
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation. https://app.cochat.ai/papers/10.1158/0008-5472.can-08-2689
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Saito, S., Furuno, A., Sakurai, J., Sakamoto, A., Park, H.-R., Shin-ya, K., Tsuruo, T., & Tomida, A. (2009). Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-2689

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