Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.
Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.
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DOI：
10.1016/j.ccr.2013.05.007
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发表时间：
2013-07-08
期刊：
影响因子：
50.3
通讯作者：
Chodosh LA
中科院分区：
文献类型：
--
作者：
Alvarez JV;Pan TC;Ruth J;Feng Y;Zhou A;Pant D;Grimley JS;Wandless TJ;Demichele A;I-SPY 1 TRIAL Investigators;Chodosh LA
大多数乳腺癌死亡是由于肿瘤复发，但肿瘤复发的机制在很大程度上是未知的。我们现在报道Par-4在肿瘤复发过程中下调，并且Par-4下调对于促进复发是必要且充分的。具有低Par-4表达的肿瘤细胞通过逃避Par-4依赖性多核化和细胞凋亡的程序而在治疗中存活，否则该程序在治疗后参与。Par-4低表达与乳腺癌患者对新辅助化疗的反应差和复发风险增加相关，并且Par-4在新辅助化疗存活的残留肿瘤细胞中下调。我们的研究结果确定Par-4诱导的多核化是癌基因成瘾细胞的细胞死亡机制，并建立了Par-4作为乳腺癌复发的负调节因子。
Most deaths from breast cancer result from tumor recurrence, but the mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is down-regulated during tumor recurrence and that Par-4 down-regulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. Low Par-4 expression is associated with poor response to neoadjuvant chemotherapy and an increased risk of relapse in breast cancer patients, and Par-4 is down-regulated in residual tumor cells that survive neoadjuvant chemotherapy. Our findings identify Par-4-induced multinucleation as a mechanism of cell death in oncogene-addicted cells and establish Par-4 as a negative regulator of breast cancer recurrence.
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影响因子：
3.8
作者：
Esserman, Laura J.;Berry, Donald A.;Cheang, Maggie C. U.;Yau, Christina;Perou, Charles M.;Carey, Lisa;DeMichele, Angela;Gray, Joe W.;Conway-Dorsey, Kathleen;Lenburg, Marc E.;Buxton, Meredith B.;Davis, Sarah E.;van't Veer, Laura J.;Hudis, Clifford;Chin, Koei;Wolf, Denise;Krontiras, Helen;Montgomery, Leslie;Tripathy, Debu;Lehman, Constance;Liu, Minetta C.;Olopade, Olufunmilayo I.;Rugo, Hope S.;Carpenter, John T.;Livasy, Chad;Dressler, Lynn;Chhieng, David;Singh, Baljit;Mies, Carolyn;Rabban, Joseph;Chen, Yunni-Yi;Giri, Dilip;Au, Alfred;Hylton, Nola
通讯作者：
Hylton, Nola
影响因子：
3.7
作者：
Vetterkind, S;Illenberger, S;Preuss, U
通讯作者：
Preuss, U
影响因子：
50.3
作者：
Moody, SE;Perez, D;Chodosh, LA
通讯作者：
Chodosh, LA
影响因子：
4.3
作者：
Mansilla, S;Priebe, W;Portugal, J
通讯作者：
Portugal, J
影响因子：
5.3
作者：
Vetterkind S;Morgan KG
通讯作者：
Morgan KG