The EMT activator ZEB1 accelerates endosomal trafficking to establish a polarity axis in lung adenocarcinoma cells.
The EMT activator ZEB1 accelerates endosomal trafficking to establish a polarity axis in lung adenocarcinoma cells.
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DOI：
10.1038/s41467-021-26677-y
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发表时间：
2021-11-03
影响因子：
16.6
通讯作者：
Kurie JM
中科院分区：
文献类型：
--
作者：
Banerjee P;Xiao GY;Tan X;Zheng VJ;Shi L;Rabassedas MNB;Guo HF;Liu X;Yu J;Diao L;Wang J;Russell WK;Roszik J;Creighton CJ;Kurie JM
上皮-间质转化（EMT）是一个转录调控的过程，癌细胞通过该过程建立了一个促进运动和侵袭的前-后极性轴。动态组装的焦点粘连和其他肌动蛋白为基础的细胞骨架结构的运动细胞的前沿需要精确的空间和时间控制蛋白质运输。然而，EMT激活转录程序与影响细胞极性变化的囊泡运输网络的相互作用方式仍不清楚。在这里，通过利用多种方法来评估囊泡运输动力学通过内吞再循环和逆行贩运途径在肺腺癌细胞在不同的位置上的EMT频谱，我们发现，EMT激活转录因子ZEB 1加速胞吞和胞内贩运质膜结合蛋白。ZEB 1通过加速受体内吞作用和转运至溶酶体区室进行降解来驱动MET受体酪氨酸激酶的周转。ZEB 1解除了一个正末端导向的微管依赖性驱动蛋白马达蛋白（KIF 13 A）和一个网格蛋白相关衔接蛋白复合物亚基（AP 1 S2）的microRNA依赖性沉默，从而分别通过内吞再循环和逆行囊泡途径加速货物运输。KIF 13 A或AP 1 S2的耗竭可减轻ZEB 1依赖性粘着斑动力学、前后轴极化和癌细胞运动性。因此，ZEB 1依赖性转录网络控制囊泡运输动力学以影响细胞极性变化。转移性肿瘤细胞控制内吞囊泡运输网络以建立促进运动的前后极性轴的方式仍不清楚。在这里，作者表明EMT激活剂ZEB 1影响囊泡运输动力学以执行细胞极性变化。
Epithelial-to-mesenchymal transition (EMT) is a transcriptionally governed process by which cancer cells establish a front-rear polarity axis that facilitates motility and invasion. Dynamic assembly of focal adhesions and other actin-based cytoskeletal structures on the leading edge of motile cells requires precise spatial and temporal control of protein trafficking. Yet, the way in which EMT-activating transcriptional programs interface with vesicular trafficking networks that effect cell polarity change remains unclear. Here, by utilizing multiple approaches to assess vesicular transport dynamics through endocytic recycling and retrograde trafficking pathways in lung adenocarcinoma cells at distinct positions on the EMT spectrum, we find that the EMT-activating transcription factor ZEB1 accelerates endocytosis and intracellular trafficking of plasma membrane-bound proteins. ZEB1 drives turnover of the MET receptor tyrosine kinase by hastening receptor endocytosis and transport to the lysosomal compartment for degradation. ZEB1 relieves a plus-end-directed microtubule-dependent kinesin motor protein (KIF13A) and a clathrin-associated adaptor protein complex subunit (AP1S2) from microRNA-dependent silencing, thereby accelerating cargo transport through the endocytic recycling and retrograde vesicular pathways, respectively. Depletion of KIF13A or AP1S2 mitigates ZEB1-dependent focal adhesion dynamics, front-rear axis polarization, and cancer cell motility. Thus, ZEB1-dependent transcriptional networks govern vesicular trafficking dynamics to effect cell polarity change. The way in which metastatic tumour cells control endocytic vesicular trafficking networks to establish a front-rear polarity axis that facilitates motility remains unclear. Here, the authors show that the EMT activator ZEB1 influences vesicular trafficking dynamics to execute cell polarity change.
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DOI：
10.1083/jcb.200911024
发表时间：
2010-08-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Friedman JR;Webster BM;Mastronarde DN;Verhey KJ;Voeltz GK
通讯作者：
Voeltz GK
影响因子：
1.9
作者：
Horzum, Utku;Ozdil, Berrin;Pesen-Okvur, Devrim
通讯作者：
Pesen-Okvur, Devrim
影响因子：
4
作者：
Dillekas, Hanna;Rogers, Michael S.;Straume, Oddhjorn
通讯作者：
Straume, Oddhjorn
DOI：
10.1016/j.biocel.2014.01.009
发表时间：
2014-04-01
影响因子：
4
作者：
Barrow-McGee, Rachel;Kermorgant, Stephanie
通讯作者：
Kermorgant, Stephanie
影响因子：
64.5
作者：
Etienne-Manneville, S;Hall, A
通讯作者：
Hall, A