In today’s new issue of JCB, Sugiyama et al. reveal that the matrix metalloprotease MT1 regulates cancer cell invasion by cleaving the receptor tyrosine kinase EphA2. The cleavage, and subsequent internalization of EphA2 initiates a Rho-dependent signaling pathway that prompts cells to roundup and detach from their neighbors, promoting their ability to disseminate from tumors as individual cells instead of invading as a cell collective. More here.
Morais da Silva et al. reveal that the spindle checkpoint protein Bub3 suppresses tumor development independently of its role in chromosome segregation. Fly cells lacking Bub3 hyperproliferate and form tumors as long as they’re prevented from undergoing apoptosis. But cells in which Bub3 is merely displaced from kinetochores – inhibiting the spindle assembly checkpoint and inducing chromosome mis-segregation – don’t form tumors. As explained here, this suggests that cytoplasmic Bub3 has an additional function that limits cell proliferation.
Upadhyay et al. describe how a protein called Sanpodo regulates the fate of fly sensory organ precursor cells. Sanpodo boosts Notch signaling in some precursor cells by binding to the γ-secretase complex that cleaves and activates the Notch receptor. In other progenitors, however, Sanpodo suppresses Notch signaling by removing the receptor from the plasma membrane. You can learn more in this week’s In Focus.
Elsewhere, Zhong et al. reveal how an excess of replication forks can slow the rate of DNA synthesis, whereas reduced replication origin firing leads to faster rates of replication. As explained in this summary, this suggests that individual forks compete for essential replication factors and nucleotides. And Bergoglio et al. describe how DNA polymerase η helps replicate problematic regions of the genome, thereby preventing chromosomal rearrangements that can drive tumorigenesis. You can learn more about this paper by listening to this month’s biobytes podcast, which features an interview with the study’s senior author Jean-Sébastien Hoffmann. You can also hear Julie Donaldson discuss her lab’s recent paper (Maldonado-Báez et al.) describing how cells rapidly sort and recycle membrane proteins internalized by clathrin-independent endocytosis.
That’s all for today, but you can find the full list of today’s new papers by visiting our table of contents here.
Cover image of a Drosophila pupa expressing a GFP fusion protein in its peripheral nervous system © 2013 Upadhyay et al.