Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation
Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation
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致癌 Ras 在有丝分裂变圆和重新扩散过程中解除细胞与基质相互作用的调节，从而改变细胞分裂方向
DOI：
10.1101/2023.01.12.523730
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ganguli S
中科院分区：
文献类型：
--
作者：
Ganguli S
致癌 Ras 已被证明可以通过增加有丝分裂过程中产生的力来改变癌细胞分裂的方式。通过这种方式，RasV12 使癌细胞能够在比正常细胞更广泛的机械环境中分裂。在这里，我们通过证明 RasV12 表达改变细胞退出有丝分裂时的形状、分裂方向和重新扩散动力学，确定了致癌 Ras-ERK 信号在分裂中的进一步作用。其中许多效应似乎是由于 RasV12 信号传导对肌动球蛋白收缩性的影响所致，因为 RasV12 会诱导通常引导纺锤体定位并提供间期细胞形状记忆的回缩纤维的切断。为了支持这一观点，RasV12表型通过抑制肌动球蛋白收缩性而逆转，并且可以通过有丝分裂期间细胞与基质粘附力的丧失来模拟。最后，我们发现 RasV12 激活还会扰乱 2D 上皮单层和 3D 球体中培养的细胞的分裂方向。因此，致癌 Ras-ERK 信号传导的诱导导致分裂方向的快速变化，再加上 RasV12 对细胞生长和细胞周期进展的影响，可能会破坏上皮组织组织并导致癌症扩散。
Oncogenic Ras has been shown to change the way cancer cells divide by increasing the forces generated during mitotic rounding. In this way, RasV12enables cancer cells to divide across a wider range of mechanical environments than normal cells. Here, we identify a further role for oncogenic Ras-ERK signaling in division by showing that RasV12expression alters the shape, division orientation, and respreading dynamics of cells as they exit mitosis. Many of these effects appear to result from the impact of RasV12signaling on actomyosin contractility, because RasV12induces the severing of retraction fibers that normally guide spindle positioning and provide a memory of the interphase cell shape. In support of this idea, the RasV12phenotype is reversed by inhibition of actomyosin contractility and can be mimicked by the loss of cell-substrate adhesion during mitosis. Finally, we show that RasV12activation also perturbs division orientation in cells cultured in 2D epithelial monolayers and 3D spheroids. Thus, the induction of oncogenic Ras-ERK signaling leads to rapid changes in division orientation that, along with the effects of RasV12on cell growth and cell-cycle progression, are likely to disrupt epithelial tissue organization and contribute to cancer dissemination.
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癌症基因组地图集中的致癌信号通路。
影响因子：
64.5
作者：
Sanchez-Vega F;Mina M;Armenia J;Chatila WK;Luna A;La KC;Dimitriadoy S;Liu DL;Kantheti HS;Saghafinia S;Chakravarty D;Daian F;Gao Q;Bailey MH;Liang WW;Foltz SM;Shmulevich I;Ding L;Heins Z;Ochoa A;Gross B;Gao J;Zhang H;Kundra R;Kandoth C;Bahceci I;Dervishi L;Dogrusoz U;Zhou W;Shen H;Laird PW;Way GP;Greene CS;Liang H;Xiao Y;Wang C;Iavarone A;Berger AH;Bivona TG;Lazar AJ;Hammer GD;Giordano T;Kwong LN;McArthur G;Huang C;Tward AD;Frederick MJ;McCormick F;Meyerson M;Cancer Genome Atlas Research Network;Van Allen EM;Cherniack AD;Ciriello G;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1101/2022.01.30.478396
发表时间：
2022-01
影响因子：
11.1
作者：
Ana Lisica;J. Fouchard;M. Kelkar;T. Wyatt;J. Duque;Anne-Betty Ndiaye;A. Bonfanti;B. Baum;A. Kabla;G. Charras
通讯作者：
Ana Lisica;J. Fouchard;M. Kelkar;T. Wyatt;J. Duque;Anne-Betty Ndiaye;A. Bonfanti;B. Baum;A. Kabla;G. Charras
影响因子：
11.2
作者：
L. Tait;H. Soule;J. Russo
通讯作者：
L. Tait;H. Soule;J. Russo
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
ERK-MAPK通过激活Wave2调节复合物来驱动层状脂蛋白突出。
影响因子：
16
作者：
Mendoza MC;Er EE;Zhang W;Ballif BA;Elliott HL;Danuser G;Blenis J
通讯作者：
Blenis J