Endocrine resistance and breast cancer plasticity are controlled by CoREST.
Endocrine resistance and breast cancer plasticity are controlled by CoREST.
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DOI：
10.1038/s41594-022-00856-x
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发表时间：
2022-11
影响因子：
16.8
通讯作者：
Morey, Lluis
中科院分区：
文献类型：
--
作者：
Garcia-Martinez, Liliana;Adams, Andrew M.;Chan, Ho Lam;Nakata, Yuichiro;Weich, Natalia;Stransky, Stephanie;Zhang, Zhao;Alshalalfa, Mohamed;Sarria, Leonor;Mahal, Brandon A.;Kesmodel, Susan B.;Celia-Terrassa, Toni;Liu, Zhijie;Minucci, Saverio;Bilbao, Daniel;Sidoli, Simone;Verdun, Ramiro E.;Morey, Lluis
对癌症治疗的耐药性仍然是一个主要的临床障碍。在这里，我们证明CoREST复合体是内分泌抵抗和ER+乳腺癌可塑性的关键决定因素。在内分泌敏感细胞中，CoREST被募集到ERα/FOXA1共结合调控区，调控雌激素通路。相反，在向抗性状态的时间重编程过程中，CoREST被招募到AP-1位点。在重编程细胞中，CoREST通过控制SWI/SNF募集而独立于CoREST亚基LSD1的去甲基化酶活性，促进染色质打开、cJUN与染色质结合和基因激活。遗传和药理学抑制CoREST可减少内分泌敏感和耐药异种移植模型的肿瘤发生和转移。一致地，CoREST控制着临床乳腺肿瘤中对涉及侵袭性的内分泌治疗产生抗性的基因特征。我们的研究揭示了CoREST的功能可以驱动细胞可塑性和对内分泌治疗和肿瘤发生的抵抗，从而确立了CoREST作为治疗晚期乳腺癌的潜在治疗靶点。
Resistance to cancer treatment remains a major clinical hurdle. Here, we demonstrate that the CoREST complex is a key determinant for endocrine resistance and ER+ breast cancer plasticity. In endocrine sensitive cells, CoREST is recruited to ERα/FOXA1 co-bound regulatory regions to regulate the estrogen pathway. In contrast, during temporal reprogramming towards a resistant state, CoREST is recruited to AP-1 sites. In reprogrammed cells, CoREST favors chromatin opening, cJUN binding to chromatin, and gene activation by controlling SWI/SNF recruitment independently of the demethylase activity of the CoREST subunit, LSD1. Genetic and pharmacological CoREST inhibition reduce tumorigenesis and metastasis of endocrine sensitive and resistant xenografts models. Consistently, CoREST controls a gene signature in clinical breast tumors resistant to endocrine therapies involved in invasiveness. Our studies reveal CoREST functions that are co-opted to drive cellular plasticity and resistance to endocrine therapies and tumorigenesis, thus establishing CoREST as a potential therapeutic target for the treatment of advanced breast cancer.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Kalin JH;Wu M;Gomez AV;Song Y;Das J;Hayward D;Adejola N;Wu M;Panova I;Chung HJ;Kim E;Roberts HJ;Roberts JM;Prusevich P;Jeliazkov JR;Roy Burman SS;Fairall L;Milano C;Eroglu A;Proby CM;Dinkova-Kostova AT;Hancock WW;Gray JJ;Bradner JE;Valente S;Mai A;Anders NM;Rudek MA;Hu Y;Ryu B;Schwabe JWR;Mattevi A;Alani RM;Cole PA
通讯作者：
Cole PA
DOI：
10.1073/pnas.1620993114
发表时间：
2017-05-30
影响因子：
11.1
作者：
Jeselsohn, Rinath;Cornwell, MacIntosh;Brown, Myles
通讯作者：
Brown, Myles