当前位置: X-MOL 学术Mol. Cancer Ther. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
AKT1low quiescent cancer cells promote solid tumor growth
Molecular Cancer Therapeutics ( IF 5.7 ) Pub Date : 2017-10-20 , DOI: 10.1158/1535-7163.mct-16-0868
Cleidson P. Alves , Ipsita Dey-Guha , Sheheryar Kabraji , Albert C. Yeh , Nilesh P. Talele , Xavier Solé , Joeeta Chowdhury , Mari Mino-Kenudson , Massimo Loda , Dennis Sgroi , Anne-Lise Borresen-Dale , Hege G. Russnes , Kenneth N. Ross , Sridhar Ramaswamy

Human tumor growth depends on rapidly dividing cancer cells driving population expansion. Even advanced tumors, however, contain slowly proliferating cancer cells for reasons that remain unclear. Here, we selectively disrupt the ability of rapidly proliferating cancer cells to spawn AKT1low daughter cells that are rare, slowly proliferating, tumor-initiating, and chemotherapy-resistant, using β1-integrin activation and the AKT1-E17K–mutant oncoprotein as experimental tools in vivo. Surprisingly, we find that selective depletion of AKT1low slow proliferators actually reduces the growth of a molecularly diverse panel of human cancer cell xenograft models without globally altering cell proliferation or survival in vivo. Moreover, we find that unusual cancer patients with AKT1-E17K–mutant solid tumors also fail to produce AKT1low quiescent cancer cells and that this correlates with significantly prolonged survival after adjuvant treatment compared with other patients. These findings support a model whereby human solid tumor growth depends on not only rapidly proliferating cancer cells but also on the continuous production of AKT1low slow proliferators. Mol Cancer Ther; 17(1); 254–63. ©2017 AACR.

中文翻译:

AKT1low 静止癌细胞促进实体瘤生长

人类肿瘤的生长依赖于快速分裂的癌细胞驱动种群扩张。然而,由于尚不清楚的原因,即使是晚期肿瘤也含有缓慢增殖的癌细胞。在这里,我们使用 β1-整合素激活和 AKT1-E17K 突变癌蛋白作为实验工具,选择性地破坏快速增殖的癌细胞产生 AKT1low 子细胞的能力,这些子细胞是罕见的、缓慢增殖的、肿瘤起始的和化疗耐药的。活体。令人惊讶的是,我们发现 AKT1low 缓慢增殖因子的选择性消耗实际上减少了一组分子多样化的人类癌细胞异种移植模型的生长,而不会全面改变体内细胞增殖或存活。而且,我们发现患有 AKT1-E17K 突变实体瘤的罕见癌症患者也无法产生 AKT1low 的静止癌细胞,这与辅助治疗后与其他患者相比显着延长的生存期有关。这些发现支持了一种模型,即人类实体瘤的生长不仅依赖于快速增殖的癌细胞,还依赖于 AKT1low 缓慢增殖细胞的持续产生。摩尔癌症治疗; 17(1); 254-63。©2017 AACR。
更新日期:2017-10-20
down
wechat
bug