Cells in the polyaneuploid cancer cell (PACC) state have increased metastatic potential.
Cells in the polyaneuploid cancer cell (PACC) state have increased metastatic potential.
复制标题
多层癌细胞（PACC）状态中的细胞具有增加的转移潜力。
DOI：
10.1007/s10585-023-10216-8
复制
发表时间：
2023-08
影响因子：
4
通讯作者：
Amend, Sarah R. R.
中科院分区：
文献类型：
--
作者：
Mallin, Mikaela M. M.;Kim, Nicholas;Choudhury, Mohammad Ikbal;Lee, Se Jong;An, Steven S. S.;Sun, Sean X. X.;Konstantopoulos, Konstantinos;Pienta, Kenneth J. J.;Amend, Sarah R. R.
关键词：
虽然转移是癌症死亡的主要原因，但在细胞水平上是相当罕见的。只有罕见的癌细胞亚群(~ 1/15亿)才能完成整个转移级联：侵袭、内渗、循环存活、外渗和定植(即具有转移能力)。我们认为具有多非整倍体癌细胞(PACC)表型的细胞具有转移能力。处于PACC状态的细胞是扩大的、内周期(即未分裂)的细胞，其基因组含量增加是对压力的反应。使用时间推移显微镜进行单细胞跟踪显示，PACC状态细胞的运动性增加。此外，处于PACC状态的细胞在趋化环境中表现出更强的环境感知和定向迁移能力，预示着成功的侵袭。磁扭转细胞术和原子力显微镜显示，处于PACC状态的细胞表现出超弹性性质，如增加的外周变形能力和维持核周皮质的完整性，这预示着成功的血管内和外渗。此外，四种正交方法显示，处于PACC状态的细胞增加了波形蛋白的表达，波形蛋白是一种已知的调节生物力学特性和诱导间充质样运动的超弹性生物分子。综上所述，这些数据表明处于PACC状态的细胞具有更高的转移潜能，值得进一步在体内进行分析。网上版载有补充材料，可在10.1007/s10585-023-10216-8查阅。
Although metastasis is the leading cause of cancer deaths, it is quite rare at the cellular level. Only a rare subset of cancer cells (~ 1 in 1.5 billion) can complete the entire metastatic cascade: invasion, intravasation, survival in the circulation, extravasation, and colonization (i.e. are metastasis competent). We propose that cells engaging a Polyaneuploid Cancer Cell (PACC) phenotype are metastasis competent. Cells in the PACC state are enlarged, endocycling (i.e. non-dividing) cells with increased genomic content that form in response to stress. Single-cell tracking using time lapse microscopy reveals that PACC state cells have increased motility. Additionally, cells in the PACC state exhibit increased capacity for environment-sensing and directional migration in chemotactic environments, predicting successful invasion. Magnetic Twisting Cytometry and Atomic Force Microscopy reveal that cells in the PACC state display hyper-elastic properties like increased peripheral deformability and maintained peri-nuclear cortical integrity that predict successful intravasation and extravasation. Furthermore, four orthogonal methods reveal that cells in the PACC state have increased expression of vimentin, a hyper-elastic biomolecule known to modulate biomechanical properties and induce mesenchymal-like motility. Taken together, these data indicate that cells in the PACC state have increased metastatic potential and are worthy of further in vivo analysis. The online version contains supplementary material available at 10.1007/s10585-023-10216-8.
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影响因子：
9.7
作者：
Amend SR;Roy S;Brown JS;Pienta KJ
通讯作者：
Pienta KJ
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
DOI：
10.1158/1541-7786.mcr-16-0436
发表时间：
2017-04
期刊：
Molecular cancer research : MCR
影响因子：
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作者：
de Groot AE;Roy S;Brown JS;Pienta KJ;Amend SR
通讯作者：
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影响因子：
4.6
作者：
Hecht, Inbal;Bar-El, Yasmin;Ben-Jacob, Eshel
通讯作者：
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影响因子：
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作者：
Fei, Fei;Zhang, Mingqing;Zhang, Shiwu
通讯作者：
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