Abstract：
:The Ras/PI3K/extracellular signal-regulated kinases (ERK) signaling network plays fundamental roles in cell growth, survival, and migration and is frequently activated in cancer. Here, we show that the activities of the signaling network propagate as coordinated waves, biased by growth factor, which drive actin-based protrusions in human epithelial cells. The network exhibits hallmarks of biochemical excitability: the annihilation of oppositely directed waves, all-or-none responsiveness, and refractoriness. Abrupt perturbations to Ras, PI(4,5)P2, PI(3,4)P2, ERK, and TORC2 alter the threshold, observations that define positive and negative feedback loops within the network. Oncogenic transformation dramatically increases the wave activity, the frequency of ERK pulses, and the sensitivity to EGF stimuli. Wave activity was progressively enhanced across a series of increasingly metastatic breast cancer cell lines. The view that oncogenic transformation is a shift to a lower threshold of excitable Ras/PI3K/ERK network, caused by various combinations of genetic insults, can facilitate the assessment of cancer severity and effectiveness of interventions.
journal_name
Dev Celljournal_title
Developmental cellauthors
Zhan H,Bhattacharya S,Cai H,Iglesias PA,Huang CH,Devreotes PNdoi
10.1016/j.devcel.2020.08.001subject
Has Abstractpub_date
2020-09-14 00:00:00pages
608-623.e5issue
5eissn
1534-5807issn
1878-1551pii
S1534-5807(20)30599-2journal_volume
54pub_type
杂志文章abstract：:Although we know that mesenchymal progenitors give rise to nephrons in the kidney, how they balance self-renewal versus differentiation is still unclear. In this issue of Developmental Cell, Chen et al. (2015) show that nephron progenitors age, but not necessarily irreversibly: old progenitors can be "rejuvenated" by ...
journal_title：Developmental cell
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journal_title：Developmental cell
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pub_type： 评论,杂志文章
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