Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype.
Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype.
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DOI：
10.3390/ijms22116161
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发表时间：
2021-06-07
影响因子：
5.6
通讯作者：
Jang HL
中科院分区：
文献类型：
--
作者：
Dash C;Saha T;Sengupta S;Jang HL
肿瘤细胞与血管的相互作用是癌症转移过程中的关键步骤之一。转移性癌细胞在这种相互作用过程中表现出表型状态的变化：（1）它们与内皮细胞形成隧道纳米管（TNT），充当细胞间通讯的管道； (2)转移性癌细胞发生变化以获得细长的表型，而不是在三维培养物中形成的经典细胞聚集体或乳腺球状结构。在这里，我们从机制上证明了基于 siRNA 的外囊复合蛋白 Sec3 敲低可抑制 TNT 形成。此外，引入了一组 Rho GTPase-胞外囊复合物介导的细胞骨架重塑的药理学抑制剂，其抑制 TNT 形成，并诱导癌细胞更具侵袭性的表型（纺锤状）逆转为侵袭性较小的表型（细胞聚集体或乳腺球）。我们的结果为癌症与内皮相互作用过程中的纳米级通讯和表型状态的转变提供了机制见解。
The interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communication; and (2) metastatic cancer cells change in order to acquire an elongated phenotype, instead of the classical cellular aggregates or mammosphere-like structures, which it forms in three-dimensional cultures. Here, we demonstrate mechanistically that a siRNA-based knockdown of the exocyst complex protein Sec3 inhibits TNT formation. Furthermore, a set of pharmacological inhibitors for Rho GTPase–exocyst complex-mediated cytoskeletal remodeling is introduced, which inhibits TNT formation, and induces the reversal of the more invasive phenotype of cancer cell (spindle-like) into a less invasive phenotype (cellular aggregates or mammosphere). Our results offer mechanistic insights into this nanoscale communication and shift of phenotypic state during cancer–endothelial interactions.
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影响因子：
7.3
作者：
Errede M;Mangieri D;Longo G;Girolamo F;de Trizio I;Vimercati A;Serio G;Frei K;Perris R;Virgintino D
通讯作者：
Virgintino D
影响因子：
4.6
作者：
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通讯作者：
Sengupta, Shiladitya
影响因子：
11.4
作者：
Fukai, S;Matern, HT;Brunger, AT
通讯作者：
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影响因子：
7.5
作者：
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通讯作者：
Carvalho, Raquel Negrao
影响因子：
3.7
作者：
Lou E;Fujisawa S;Morozov A;Barlas A;Romin Y;Dogan Y;Gholami S;Moreira AL;Manova-Todorova K;Moore MA
通讯作者：
Moore MA