CDK4 regulates cancer stemness and is a novel therapeutic target for triple-negative breast cancer.
CDK4 regulates cancer stemness and is a novel therapeutic target for triple-negative breast cancer.
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DOI：
10.1038/srep35383
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发表时间：
2016-10-19
影响因子：
4.6
通讯作者：
Lebrun JJ
中科院分区：
文献类型：
--
作者：
Dai M;Zhang C;Ali A;Hong X;Tian J;Lo C;Fils-Aimé N;Burgos SA;Ali S;Lebrun JJ
三阴性乳腺癌表现出非常侵袭性的特征和较差的患者结局。这些肿瘤富含癌症干细胞，并对大多数治疗和化疗表现出抗性。在这项研究中，我们发现细胞周期蛋白依赖性激酶（CDK 4）在三阴性乳腺癌中作为癌症干细胞调节因子和新的预后标志物。我们发现CDK 4在这些肿瘤中高度表达，并且其表达与三阴性乳腺癌患者的总体和无复发生存结局差、肿瘤分级高和预后不良特征相关。此外，我们发现，使用药理学抑制剂阻断CDK 4表达或激酶活性可阻止乳腺癌干细胞自我更新。有趣的是，CDK 4表达或激酶活性的抑制将基底-B TNBC间充质表型逆转为上皮样和管腔样表型，这与更好的临床预后相关。最后，阻断CDK 4活性有效地消除了三阴性乳腺癌中的正常和化疗耐药癌细胞，突出了CDK 4作为这些侵袭性乳腺肿瘤的有希望的新型治疗靶点。
Triple negative breast cancers exhibit very aggressive features and poor patient outcomes. These tumors are enriched in cancer stem cells and exhibit resistance to most treatments and chemotherapy. In this study, we found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. We found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients. Moreover, we found that blocking CDK4 expression or kinase activity, using a pharmacological inhibitor prevented breast cancer stem cell self-renewal. Interestingly, suppression of CDK4 expression or kinase activity reversed the basal-B TNBC mesenchymal phenotype to an epithelial- and luminal-like phenotype which correlates with better clinical prognosis. Finally, blocking CDK4 activity efficiently eliminated both normal and chemotherapy-resistant cancer cells in triple negative breast cancers, highlighting CDK4 as a promising novel therapeutic target for these aggressive breast tumors.
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CD44+ CD24（ - ）前列腺细胞是早期的癌症祖/干细胞，为预后不良的患者提供了模型。
影响因子：
8.8
作者：
Hurt, E. M.;Kawasaki, B. T.;Klarmann, G. J.;Thomas, S. B.;Farrar, W. L.
通讯作者：
Farrar, W. L.
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
64.8
作者：
通讯作者：
--
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
DOI：
10.1186/bcr3441
发表时间：
2013-06-20
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dai M;Al-Odaini AA;Fils-Aimé N;Villatoro MA;Guo J;Arakelian A;Rabbani SA;Ali S;Lebrun JJ
通讯作者：
Lebrun JJ