JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance.
JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance.
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JAK/STAT3调节的脂肪酸β-氧化对于乳腺癌干细胞的自我更新和化学抗性至关重要。
DOI：
10.1016/j.cmet.2017.11.001
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发表时间：
2018-01-09
期刊：
影响因子：
29
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Wang T;Fahrmann JF;Lee H;Li YJ;Tripathi SC;Yue C;Zhang C;Lifshitz V;Song J;Yuan Y;Somlo G;Jandial R;Ann D;Hanash S;Jove R;Yu H
癌症干细胞（CSCs）是癌症进展和化疗耐药的关键。脂质代谢如何调节CSCs和化疗耐药仍然是未知的。在这里，我们证明JAK/STAT3调节脂质代谢，从而促进乳腺CSCs （BCSCs）和癌症化疗耐药。抑制JAK/STAT3阻断BCSC自我更新和多种脂质代谢基因的表达，包括肉碱棕榈酰基转移酶1B (CPT1B)，该基因编码脂肪酸β-氧化（FAO）的关键酶。此外，乳腺脂肪细胞来源的瘦素上调stat3诱导的BCSCs中CPT1B的表达和FAO活性。人类乳腺癌来源的数据表明STAT3-CPT1B-FAO通路促进癌细胞干细胞和化疗耐药。阻断FAO和/或瘦素可使它们对化疗再敏感，并在体内抑制小鼠乳腺肿瘤中的BCSCs。我们确定了BCSC维持和乳腺癌化疗耐药的关键途径。肿瘤干细胞在肿瘤发展和化疗耐药中起着重要作用。Wang等研究表明，leptin-JAK/STAT3通过脂肪酸β-氧化（fatty acid β-oxidation， FAO）调节脂质代谢，促进乳腺癌的发生和化疗耐药。阻断FAO和/或消耗瘦素可使癌细胞对化疗重新敏感，同时降低体内癌症的发生率。
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. Cancer stem cells play an important role in cancer development and chemoresistance. Wang et al. show that leptin-JAK/STAT3 regulates lipid metabolism through fatty acid β-oxidation (FAO), promoting breast cancer stemness and chemoresistance. Blocking FAO and/or depleting leptin re-sensitize cancer cells to chemotherapy while reducing cancer stemness in vivo.
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DOI：
10.1016/j.bbalip.2013.03.011
发表时间：
2013-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Baumann J;Sevinsky C;Conklin DS
通讯作者：
Conklin DS
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
15.9
作者：
Carracedo, Arkaitz;Weiss, Dror;Pandolfi, Pier P.
通讯作者：
Pandolfi, Pier P.
影响因子：
64.5
作者：
Ho PC;Bihuniak JD;Macintyre AN;Staron M;Liu X;Amezquita R;Tsui YC;Cui G;Micevic G;Perales JC;Kleinstein SH;Abel ED;Insogna KL;Feske S;Locasale JW;Bosenberg MW;Rathmell JC;Kaech SM
通讯作者：
Kaech SM