Highlights d The monopolar-to-bipolar spindle transition is fast and irreversible d The fast transition is driven by Cin8 (Kinesin-5) microtubule crosslinking d Nascent bipolar spindles need Kinesin-5 sliding for steadystate lengths >1 mm d Spindle formation sequentially integrates Kinesin-5 MT crosslinking and sliding

Highlights d aand b-tubulins are the core components of microtubules d Yeast-carrying mutations in b-tubulin are hypersensitive to DNA replication stress d Microtubules are essential to limit the effects of replication stress to S phase d b-tubulin modulates sister kinetochore tension following DNA replication stress

a metastatic variant of MDA-MB-231 cells with b-adrenergic agonist. We determine changes in subcellular structure by immunofluorescence and quantitative image analysis, and measure cell deformability using parallel microfiltration. b-adrenoreceptor activation by isoproterenol decreases cell deformability significantly. We observe that treatment with isoproterenol increases elongated protrusions and alters the distribution of cytoplasmic F-actin, suggesting that changes in F-actin polymerization may contribute to decreased deformability. Our observations warrant further in vitro and in vivo investigation of the underlying mechanisms by which b-adrenoreceptor activation mediates changes in the biophysical properties of breast cancer cells and consequently regulates metastasis of the disease. Identifying the molecular pathways that are implicated in b-adrenergic signaling-induced changes of cell deformability will inform additional strategies for antimetastatic therapies of primary breast cancers.

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