Factor quinolinone inhibitors alter cell morphology and motility by destabilizing interphase microtubules.
Factor quinolinone inhibitors alter cell morphology and motility by destabilizing interphase microtubules.
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DOI：
10.1038/s41598-021-02962-0
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发表时间：
2021-12-07
影响因子：
4.6
通讯作者：
Hansen U
中科院分区：
文献类型：
--
作者：
Stoiber P;Scribani Rossi P;Pokharel N;Germany JL;York EA;Schaus SE;Hansen U
喹啉酮抑制剂是一类很有前途的抗癌化合物，最初被认为是致癌转录因子LSF（TFCP 2）的特异性抑制剂。这些化合物至少部分通过破坏有丝分裂纺锤体来发挥抗增殖活性。在此，我们报告额外的间期后果的最初的铅化合物，MARI 1，在两个端粒酶永生化细胞系。在添加CITI 1的几分钟内，微管网络被破坏，导致微管大量（尽管不完全）耗尽，这一点通过微管沉降测定和显微镜检查都得到了证明。令人惊讶的是，这种微管分解很快就伴随着剩余微管中微管蛋白乙酰化的增加。微管网络的突然破裂和部分解聚先于PAI 1诱导的形态学变化。这些包括间期胎肝细胞的细胞铺展迅速减少和视网膜色素上皮细胞的圆形度增加。微管解聚导致FH-B细胞致密化，因为紫杉醇预处理阻止了这种形态学变化。最后，BRI 1降低间期细胞运动的速率和范围，支持BRI 1诱导的微管断裂对细胞运动的影响。两者合计，我们的研究结果表明，干扰微管相关的功能，在间期，特别是细胞形态和运动。
Factor quinolinone inhibitors are promising anti-cancer compounds, initially characterized as specific inhibitors of the oncogenic transcription factor LSF (TFCP2). These compounds exert anti-proliferative activity at least in part by disrupting mitotic spindles. Herein, we report additional interphase consequences of the initial lead compound, FQI1, in two telomerase immortalized cell lines. Within minutes of FQI1 addition, the microtubule network is disrupted, resulting in a substantial, although not complete, depletion of microtubules as evidenced both by microtubule sedimentation assays and microscopy. Surprisingly, this microtubule breakdown is quickly followed by an increase in tubulin acetylation in the remaining microtubules. The sudden breakdown and partial depolymerization of the microtubule network precedes FQI1-induced morphological changes. These involve rapid reduction of cell spreading of interphase fetal hepatocytes and increase in circularity of retinal pigment epithelial cells. Microtubule depolymerization gives rise to FH-B cell compaction, as pretreatment with taxol prevents this morphological change. Finally, FQI1 decreases the rate and range of locomotion of interphase cells, supporting an impact of FQI1-induced microtubule breakdown on cell motility. Taken together, our results show that FQI1 interferes with microtubule-associated functions in interphase, specifically cell morphology and motility.
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DOI：
10.1083/jcb.200902128
发表时间：
2009-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Klebig C;Korinth D;Meraldi P
通讯作者：
Meraldi P
影响因子：
18.4
作者：
Gandalovičová A;Rosel D;Fernandes M;Veselý P;Heneberg P;Čermák V;Petruželka L;Kumar S;Sanz-Moreno V;Brábek J
通讯作者：
Brábek J
微管蛋白代码：分子成分、读出机制和功能。
DOI：
10.1083/jcb.201406055
发表时间：
2014-08-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Janke C
通讯作者：
Janke C
影响因子：
3.3
作者：
Chang, Yuan-Chen;Nalbant, Perihan;Bokoch, Gary M.
通讯作者：
Bokoch, Gary M.
DOI：
10.1073/pnas.1605397113
发表时间：
2016-11-15
影响因子：
11.1
作者：
Coombes, Courtney;Yamamoto, Ami;Gardner, Melissa K.
通讯作者：
Gardner, Melissa K.