| First Author | Wang T | Year | 2018 |
| Journal | Cell Metab | Volume | 27 |
| Issue | 1 | Pages | 136-150.e5 |
| PubMed ID | 29249690 | Mgi Jnum | J:256882 |
| Mgi Id | MGI:6115157 | Doi | 10.1016/j.cmet.2017.11.001 |
| Citation | Wang T, et al. (2018) JAK/STAT3-Regulated Fatty Acid beta-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance. Cell Metab 27(1):136-150.e5 |
| abstractText | 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 beta-oxidation (FAO). Moreover, mammary-adipocyte-derived leptin upregulates STAT3-induced CPT1B expression and FAO activity in BCSCs. Human breast-cancer-derived data suggest that the 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. |
