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Cited by 825

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JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance

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Wang, Tianyi, Fahrmann, Johannes Francois, Lee, Heehyoung, Li, Yi-Jia, Tripathi, Satyendra C., Yue, Chanyu, Zhang, Chunyan, Lifshitz, Veronica, Song, Jieun, Yuan, Yuan, Somlo, George, Jandial, Rahul, Ann, David, Hanash, Samir, Jove, Richard, Yu, Hua·2018·Cell Metabolism
DOI 10.1016/j.cmet.2017.11.001
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Abstract

SUMMARY Cancer stem cells (CSCs) are critical for cancer progression and chemoresistance. How lipid metabolism regulates CSCs and chemoresistance remains elusive. Here, we demonstrate that JAK/STAT3 regulates lipid metabolism, which promotes breast CSCs (BCSCs) and cancer chemoresistance. Inhibiting JAK/STAT3 blocks BCSC self-renewal and expression of diverse lipid metabolic genes, including carnitine palmitoyltransferase 1B (CPT1B), which encodes the critical enzyme for fatty acid β-oxidation (FAO). Moreover, mammary adipocyte-derived leptin upregulates STAT3-induced CPT1B expression and FAO activity in BCSCs. Human breast cancer-derived data suggest STAT3-CPT1B-FAO pathway promotes cancer cell stemness and chemoresistance. Blocking FAO and/or leptin re-sensitizes them to chemotherapy and inhibits BCSCs in mouse breast tumors in vivo. We identify a critical pathway for BCSC maintenance and breast cancer chemoresistance.

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Metadata

Authors
Wang, T., Fahrmann, J. F., Lee, H., Li, Y.-J., Tripathi, S. C., Yue, C., Zhang, C., Lifshitz, V., Song, J., Yuan, Y., Somlo, G., Jandial, R., Ann, D., Hanash, S., Jove, R., & Yu, H.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2018-01
Volume
27
Issue
1
Pages
136-150.e5
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2017.11.001
OpenAlex
W2772250549
Cited by
825
References
9
FWCI
15.88
Type
journal article
Language
en
Update notices
erratum (2018-06-05)
Open access
bronze
Licence
Funders
  • Beckman Research Institute, City of Hope
  • National Cancer Institute (P30CA033572)
  • National Institutes of Health (R01CA122976)

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CoChat. (2026). Citation check: JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance. https://app.cochat.ai/papers/10.1016/j.cmet.2017.11.001
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Wang, T., Fahrmann, J. F., Lee, H., Li, Y.-J., Tripathi, S. C., Yue, C., Zhang, C., Lifshitz, V., Song, J., Yuan, Y., Somlo, G., Jandial, R., Ann, D., Hanash, S., Jove, R., & Yu, H. (2018). JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance. Cell Metabolism. https://doi.org/10.1016/j.cmet.2017.11.001

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