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Removal of senescent cells via Epithelial-to-Mesenchymal transition

Removal of senescent cells via Epithelial-to-Mesenchymal transition

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

By Shubhankar Kulkarni on 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

Juran K. a month 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?...

Shubhankar Kulkarni a month 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....