C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer.
C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer.
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DOI：
10.1038/s41467-021-27734-2
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发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Halberg N
中科院分区：
文献类型：
--
作者：
Liu XZ;Rulina A;Choi MH;Pedersen L;Lepland J;Takle ST;Madeleine N;Peters SD;Wogsland CE;Grøndal SM;Lorens JB;Goodarzi H;Lønning PE;Knappskog S;Molven A;Halberg N
流行病学研究证实，肥胖与绝经后乳腺癌的发病率之间存在正相关关系。此外，众所周知，肥胖促进了乳腺癌细胞的干细胞样特性。然而，这种相关性背后的癌细胞自主机制还没有很好的定义。在这里，我们证明了肥胖相关肿瘤的形成是由细胞适应驱动的，而不是癌细胞群体中先前存在的克隆的扩张。虽然与特定的突变没有相关性，但细胞对肥胖的适应是由棕榈酸(PA)控制的，并导致乳腺癌细胞形成肿瘤的能力增强。这一过程是通过增加转录因子CCAAT/增强子结合蛋白β(C/EBPB)的染色质占有率来表观遗传的。肥胖诱导的C/EBPB的表观遗传激活通过调节关键的下游调控因子包括CLDN1和Lcn2的表达来调节癌症干细胞样特性。总而言之，我们的发现表明，肥胖驱动细胞对PA的适应通过激活C/EBPB依赖的转录网络在肥胖环境中驱动肿瘤启动。肥胖与绝经后乳腺癌的癌症风险有关。在分子水平上，这是由细胞对棕榈酸的适应通过表观遗传激活依赖于C/EBPB的转录网络来驱动肿瘤形成的。
Epidemiological studies have established a positive association between obesity and the incidence of postmenopausal breast cancer. Moreover, it is known that obesity promotes stem cell-like properties of breast cancer cells. However, the cancer cell-autonomous mechanisms underlying this correlation are not well defined. Here we demonstrate that obesity-associated tumor formation is driven by cellular adaptation rather than expansion of pre-existing clones within the cancer cell population. While there is no correlation with specific mutations, cellular adaptation to obesity is governed by palmitic acid (PA) and leads to enhanced tumor formation capacity of breast cancer cells. This process is governed epigenetically through increased chromatin occupancy of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPB). Obesity-induced epigenetic activation of C/EBPB regulates cancer stem-like properties by modulating the expression of key downstream regulators including CLDN1 and LCN2. Collectively, our findings demonstrate that obesity drives cellular adaptation to PA drives tumor initiation in the obese setting through activation of a C/EBPB dependent transcriptional network. Obesity is linked to cancer risk in post-menopausal breast cancer. At the molecular level this is governed by cellular adaption to palmitic acid through epigenetic activation of a C/EBPB-dependent transcriptional network that drives tumor formation.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
50.3
作者：
Dravis C;Chung CY;Lytle NK;Herrera-Valdez J;Luna G;Trejo CL;Reya T;Wahl GM
通讯作者：
Wahl GM
DOI：
10.1093/annonc/mdu042
发表时间：
2014-10
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Chan DSM;Vieira AR;Aune D;Bandera EV;Greenwood DC;McTiernan A;Navarro Rosenblatt D;Thune I;Vieira R;Norat T
通讯作者：
Norat T
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
8
作者：
通讯作者：
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