Facebook PixelRemoval of senescent cells via Epithelial-to-Mesenchymal transition
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Removal of senescent cells via Epithelial-to-Mesenchymal transition

Image credit: Riki okita et al., 2018 http://jtd.amegroups.com/article/view/23392/html

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Shubhankar Kulkarni
Shubhankar Kulkarni Aug 06, 2020

[1]Maithilee Khot, Dyuthi Sreekumar, Sanika Jahagirdar, Apoorva Kulkarni, Kishore Hari, Elangoli Ebrahimkutty Faseela, Radhakrishnan Sabarinathan, Mohit Kumar Jolly, Kundan Sengupta, Twist1 induces chromosomal instability (CIN) in colorectal cancer cells, Human Molecular Genetics, Volume 29, Issue 10, 15 May 2020, Pages 1673–1688, https://doi.org/10.1093/hmg/ddaa076

[2]Okita R, Shimizu K, Nakata M. Epithelial-mesenchymal transition-induced metastasis could be a bait for natural killer cells. J Thorac Dis 2018;10(Suppl 26):S3143-S3146. doi: 10.21037/jtd.2018.08.19

General comments

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Darko Savic
Darko Savic3 months ago
I don't remember where I got this from (so no reference) but virus-infected cells are known to detach. Could we engineer an appropriate virus that will cause said detachment, to target specifically Senescent cells?
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Shubhankar Kulkarni
Shubhankar Kulkarni3 months ago
Darko Savic Great idea! Here is a reference: The Ebola virus envelope glycoprotein (GP) mediated cell detachment from the extracellular matrix in 293T cells. A reduction in cell surface expression of adhesion molecules such as integrin β1, major histocompatibility complex class I, and the epidermal growth factor receptor was observed with the loss of cell adhesion. Furthermore, the Ebola virus GP did not increase cell death while causing cell detachment. Also, the cells were able to readhere and continue to divide once the GP expression was modulated. Even the replication-deficient adenovirus vectors expressing Ebola virus GP could induce the loss of cell adhesion in endothelial cells and macrophages.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153797/
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JK
Juran K.5 months ago
Let's say we have acutely or chronically damaged cells that can either be fixed or turn apoptotic, senescent, or tumorigenic. Our cells „pick“ the road of senescence. ----- Once alive and a threat, these cells are now „put to sleep“. They still can affect aging and promote tumor development by secretion of specific factors (doi:10.1038/nrm3823, doi: 10.5772/54120), so we want them out of the system. Besides, clearing senescent cells showed a significant effect on tissue homeostasis and aging (doi:10.1016/j.cell.2017.02.031), so we are eager to remove them, possibly without „waking them up“! ----- EMT is a transition process that metabolically active and dividing cells sometimes „use“ to become motile and spread (fibrosis, metastasis). So, for that, we need cells that are „awake“ and somewhat safe, unless we want a tumor! ----- While figuring it out, I bumped on a few articles stating that some molecular mechanisms that regulate these two processes are crossing paths. Transcription factors like Twist and Zeb1 can simultaneously both inhibit senescence and induce EMT (doi:10.1038/s41420-020-0286-z, doi:10.18632/aging.100209). It would be a perfect tool for the above-mentioned idea, but could easily go wrong and promote tumor progression in “awaken” cells. -----> So, if we somehow manage to specifically target only the senescent cells in inaccessible regions of tissues and turn them motile (using Zeb1, for example), wouldn't that be the awakening of the Frankenstein? Can we perform dialysis cells faster than small Frankensteins do bigger damage, or we need a faster clearance tool, already waiting in the bloodstream?
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Shubhankar Kulkarni
Shubhankar Kulkarni5 months ago
Hi Juran! Thank you for the comment. Performing dialysis and clearing the senescent cells is the ultimate goal. For that, we need to remove the senescent cells from the inaccessible places and make them enter the bloodstream. Based on your comment, now I think we can use Twist or Zeb1 in combination with senolytics or dialysis to get the desired effect.