Metastasis is a highly stressful process.
Metastasis is a highly stressful process.
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DOI：
10.1007/s10555-020-09938-y
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Cheresh DA
中科院分区：
文献类型：
--
作者：
Campos AD;Weis SM;Cheresh DA
肿瘤的进展和转移到继发部位取决于原发肿瘤激活适应性反应的能力，以克服在原始肿瘤微环境（TME）和转移过程中遇到的细胞应激。这些适应性反应驱动表型变化，具有独特的功能，使肿瘤进展和转移。为什么一些癌细胞变得耐应激并发展为转移表型，而来自同一肿瘤的具有相似遗传背景的其他癌细胞却没有，这仍然是一个关键的未解之谜。肿瘤细胞需要多种技能才能成功地在继发性肿瘤部位定植，包括上皮细胞到间充质细胞的转化（EMT）、应激耐受性、免疫逃避和微环境的操纵。因此，转移事件只能由肿瘤内的一小部分细胞亚群执行。尽管这一转移性亚群在功能上具有独特性，但基因组研究已经报道，继发肿瘤部位的肿瘤的遗传异质性与其原发肿瘤部位[2]高度保守。因此，转移启动细胞的转移潜力不一定是由获得新的突变驱动的，而是可以通过其转录程序的剧烈变化来刺激的。我们假设TME固有的细胞应激诱导了这些转移程序。Cheresh实验室的一个重点领域是更好地了解导致转移启动细胞特性激活的细胞过程。先前的研究发现，细胞表面受体整合素αvβ3的表达是诱导转移细胞特性（包括肿瘤起始、应激耐受性和干细胞性）的必要和充分条件。事实上，整合素αvβ3是一种被广泛接受的肿瘤细胞EMT标志物。与转移亚群模式一致，αvβ3通常不在非转移性上皮癌细胞上表达，但它的表达可以通过细胞外信号诱导来驱动转移表型。机制上，αvβ3在人和小鼠耐药癌细胞上的选择性表达与αvβ3激活肿瘤细胞的能力有关
Tumor progression and metastasis to secondary sites depend on the ability of a primary tumor to activate adaptive responses to overcome cellular stresses encountered within the original tumor microenvironment (TME) and during the metastatic process. These adaptive responses drive phenotypic changes with distinct functionality to enable tumor progression and metastasis. Why some cancer cells become stress tolerant and develop a metastatic phenotype, while other cancer cells with similar genetic backgrounds from the same tumor do not, remains a critical unanswered biological question. Tumor cells call upon a variety of skills to successfully colonize a secondary tumor site, including epithelial to mesenchymal transition (EMT), stress tolerance, immune evasion, and manipulation of the microenvironment [1]. Accordingly, metastatic events can only be executed by a small subpopulation of cells within the tumor. Despite the functional uniqueness of this metastatic subpopulation, genomic studies have reported that the genetic heterogeneity of tumors located at secondary tumor sites is highly conserved with respect to their primary tumor site [2]. Thus, the metastatic potential of metastasis initiating cells is not necessarily driven by the acquisition of new mutations, but rather can be stimulated through dramatic changes in their transcriptional programs. We postulate that cellular stresses intrinsic to the TME induce these metastatic programs.One area of focus in the Cheresh laboratory is to better understand the cellular processes leading to the activation of metastasis initiating cell properties. Previous work identified expression of the cell surface receptor integrin αvβ3 as both necessary and sufficient for inducing metastatic cell properties, including tumor initiation, stress tolerance, and stemness [3]. Indeed, integrin αvβ3 is a widely accepted marker for tumor cells that have undergone EMT. Congruent with the metastatic subpopulation paradigm, αvβ3 is not normally expressed on non-metastatic epithelial cancer cells, but its expression can be induced by extracellular cues to drive a metastatic phenotype. Mechanistically, selective expression of αvβ3 on drug-resistant cancer cells in both humans and mice was associated with the ability of αvβ3 to activate the
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乳腺癌细胞中ITGB3的低氧介导的转化激活增强了TGF-β信号传导和体内的恶性特征。
影响因子：
--
作者：
Sesé M;Fuentes P;Esteve-Codina A;Béjar E;McGrail K;Thomas G;Aasen T;Ramón Y Cajal S
通讯作者：
Ramón Y Cajal S
影响因子：
19
作者：
Seguin, Laetitia;Desgrosellier, Jay S.;Weis, Sara M.;Cheresh, David A.
通讯作者：
Cheresh, David A.
影响因子：
10.5
作者：
Celià-Terrassa T;Kang Y
通讯作者：
Kang Y
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
64.8
作者：
Yachida S;Jones S;Bozic I;Antal T;Leary R;Fu B;Kamiyama M;Hruban RH;Eshleman JR;Nowak MA;Velculescu VE;Kinzler KW;Vogelstein B;Iacobuzio-Donahue CA
通讯作者：
Iacobuzio-Donahue CA