Increased cancer stem cell invasion is mediated by myosin IIB and nuclear translocation.
Increased cancer stem cell invasion is mediated by myosin IIB and nuclear translocation.
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DOI：
10.18632/oncotarget.9896
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Egelhoff T
中科院分区：
文献类型：
--
作者：
Thomas D;Thiagarajan PS;Rai V;Reizes O;Lathia J;Egelhoff T
尽管乳腺癌的治疗取得了许多进展，但它仍然是导致女性死亡的主要原因之一。有效治疗的一个障碍是治疗被称为癌症干细胞(CSCs)的高侵袭性和致瘤性肿瘤亚群。当EGF刺激时，CSCs在生理性3D胶原基质中的迁移速度比非干细胞癌细胞(Non-SCCs)更快。这种侵袭性的增加，部分是由于CSCs核转位能力的增强。我们观察到CSC和非SCC在2D表面上的细胞迁移率没有差异。此外，在使用大直径井间孔隙的井间迁移过程中，CSC和非SCC种群的迁移效率相似。然而，当面临更多限制井间的挑战时，CSCs的跨井运移能力要强得多。这些结果表明，核移位是CSC扩散的一个主要限制因素。我们进一步表明，非肌肉肌球蛋白IIB对于这种增强的核移位和癌症干细胞在限制性3D环境中高效迁移的能力至关重要。这些研究表明，在CSCs中上调的细胞骨架元件，如肌球蛋白IIB，可能是干预肿瘤干细胞从肿瘤扩散的有价值的靶点。
Despite many advances in the treatment of breast cancer, it remains one of the leading causes of death among women. One hurdle for effective therapy is the treatment of the highly invasive and tumorigenic subpopulation of tumors called cancer stem cells (CSCs). CSCs, when stimulated with EGF, migrate through a physiological 3D collagen matrix at a higher velocity than non-stem cancer cells (non-SCCs). This increased invasion is due, in part, by an enhanced nuclear translocation ability of CSCs. We observed no difference between CSC and non-SCC in cellular migration rates on a 2D surface. Furthermore, during transwell migration using large diameter transwell pores, both CSC and non-SCC populations migrated with similar efficiency. However, when challenged with more restrictive transwells, CSCs were dramatically more capable of transwell migration. These results implicate nuclear translocation as a major rate limiting factor for CSC dissemination. We further show that non-muscle myosin IIB is critical for this enhanced nuclear translocation and the ability for cancer stem cells to efficiently migrate through restrictive 3D environments. These studies suggest that cytoskeletal elements upregulated in CSCs, such as myosin IIB, may be valuable targets for intervention in cancer stem cell dispersal from tumors.
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影响因子：
3.3
作者：
Breckenridge, Mark T.;Dulyaninova, Natalya G.;Egelhoff, Thomas T.
通讯作者：
Egelhoff, Thomas T.
影响因子：
254.7
作者：
DeSantis, Carol;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
3.9
作者：
Zheng, Qiao;Banaszak, Lauren;Reizes, Ofer
通讯作者：
Reizes, Ofer
影响因子：
--
作者：
Franqui-Machin R;Wendlandt EB;Janz S;Zhan F;Tricot G
通讯作者：
Tricot G
影响因子：
12.4
作者：
Kim, Sang-Soo;Rait, Antonina;Chang, Esther H.
通讯作者：
Chang, Esther H.