An unexpected alliance between stress responses to drive oncogenesis.
XBP1 is a well-characterized regulator of the unfolding protein response that is activated in response to unfolded or misfolded proteins or nutrient deprivation. The conventional wisdom is that XBP1 is activated to coordinate the unfolded protein response and promote cellular survival under stresses. A recent study provides intriguing evidence that, in triple-negative breast cancer, XBP1 plays a major role in promoting oncogenesis and cancer stem cell properties. Unexpectedly, XBP1 accomplishes this by recruiting hypoxia-inducible factor 1α and activating oncogenic transcriptional programs. This study reveals a surprising hierarchy and alliance between two stress regulators with distinct transcriptional outputs to promote an aggressive oncogenic state.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, 268 CARL Building, Research Drive, Box 3054 DUMC, Durham, NC, 27710, USA. melissa.keenan@duke.edu.|Center for Genomic and Computational Biology, Duke Medical Center, 2177A CIEMAS Building, 101 Research Drive, DUMC 3382, Durham, NC, 27708, USA. melissa.keenan@duke.edu.
Melissa M
MM
Keenan
Department of Molecular Genetics and Microbiology, Duke University Medical Center, 268 CARL Building, Research Drive, Box 3054 DUMC, Durham, NC, 27710, USA. chienkuang.ding@gmail.com.|Center for Genomic and Computational Biology, Duke Medical Center, 2177A CIEMAS Building, 101 Research Drive, DUMC 3382, Durham, NC, 27708, USA. chienkuang.ding@gmail.com.
Chien-Kuang Cornelia
CK
Ding
Department of Molecular Genetics and Microbiology, Duke University Medical Center, 268 CARL Building, Research Drive, Box 3054 DUMC, Durham, NC, 27710, USA. jentsan.chi@duke.edu.|Center for Genomic and Computational Biology, Duke Medical Center, 2177A CIEMAS Building, 101 Research Drive, DUMC 3382, Durham, NC, 27708, USA. jentsan.chi@duke.edu.
Jen-Tsan
JT
Chi
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*
D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors