Cortical branched actin determines cell cycle progression

• Published in: Cell research Vol. 29; no. 6; pp. 432 - 445
• Main Authors: Molinie, Nicolas, Rubtsova, Svetlana N., Fokin, Artem, Visweshwaran, Sai P., Rocques, Nathalie, Polesskaya, Anna, Schnitzler, Anne, Vacher, Sophie, Denisov, Evgeny V., Tashireva, Lubov A., Perelmuter, Vladimir M., Cherdyntseva, Nadezhda V., Bièche, Ivan, Gautreau, Alexis M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2019; Nature Publishing Group
• Subjects: 13; 13/1; 13/89; 13/95; 14/63; 631/67/1347; 631/80/128/1276; 631/80/84/1756; Actin; Actins - metabolism; Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Biology; Cell Cycle; Cell Line, Tumor; Cell migration; Cell Movement; Cellular Biology; Chemotherapy, Adjuvant; Cohort Studies; Cortex; Cytoskeleton; Dependence; Diagnostic systems; Epithelial cells; Female; G1 phase; Growth factors; Humans; Life Sciences; Mammary gland; Mechanotransduction; Metastases; Middle Aged; Rac1 protein; Rigidity; RNA, Messenger - genetics; Subcellular Processes; Tumors
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/s41422-019-0160-9

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.