Cortical branched actin determines cell cycle progression  

作　　者：Nicolas Molinie Svetlana N. Rubtsova Artem Fokin Sai P. Visweshwaran Nathalie Rocques Anna Polesskaya Anne Schnitzler Sophie Vacher Evgeny V. Denisov Lubov A. Tashireva Vladimir M. Perelmuter Nadezhda V. Cherdyntseva Ivan Bièche Alexis M. Gautreau 

机构地区：[1]BIOC, Ecole polytechnique, CNRS, IP Paris, Palaiseau, France [2]N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia [3]Department of Genetics, Institut Curie, Paris, France [4]Tomsk National Research Medical Center, Tomsk, Russia [5]Tomsk State University, Tomsk, Russia [6]School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia

出　　处：《Cell Research》2019年第6期432-445,共14页细胞研究（英文版）

基　　金：the Agence Nationale de la Recherche (ANR- 15-CE13-0016-01 for AG);from Institut National du Cancer (INCA_6521 and INCA_11508 for AG and IB);from the fondation ARC pour la Recherche sur le Cancer (PGA120140200831 for AG and IB);Russian Science Foundation (grant #16-15-10288 for SNR);the Russian Science Foundation (grant #16-15-10221).

摘　　要：The actin cytoskeleton generates and senses forces. Here we report that branched actin networks from the cell cortex depend on ARPC1B-containing Arp2/3 complexes and that they are specifically monitored by type I coronins to control cell cycle progression in mammary epithelial cells. Cortical ARPC1B-dependent branched actin networks are regulated by the RAC1/WAVE/ARPIN pathway and drive lamellipodial protrusions. Accordingly, we uncover that the duration of the G1 phase scales with migration persistence in single migrating cells. Moreover, cortical branched actin more generally determines S-phase entry by integrating soluble stimuli such as growth factors and mechanotransduction signals, ensuing from substratum rigidity or stretching of epithelial monolayers. Many tumour cells lose this dependence for cortical branched actin. But the RAC1-transformed tumour cells stop cycling upon Arp2/3 inhibition. Among all genes encoding Arp2/3 subunits, ARPC1B overexpression in tumours is associated with the poorest metastasis-free survival in breast cancer patients. Arp2/3 specificity may thus provide diagnostic and therapeutic opportunities in cancer.

关 键 词：CYTOSKELETON FORCES cancer 

分 类 号：Q[生物学]