Cells (Aug 2023)

Deciphering the Role of p60AmotL2 in Epithelial Extrusion and Cell Detachment

  • Weiyingqi Cui,
  • Aravindh Subramani,
  • Pedro Fonseca,
  • Yumeng Zhang,
  • Le Tong,
  • Yuanyuan Zhang,
  • Lars Egevad,
  • Andreas Lundqvist,
  • Lars Holmgren

DOI
https://doi.org/10.3390/cells12172158
Journal volume & issue
Vol. 12, no. 17
p. 2158

Abstract

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Preserving an accurate cell count is crucial for maintaining homeostasis. Apical extrusion, a process in which redundant cells are eliminated by neighboring cells, plays a key role in this regard. Recent studies have revealed that apical extrusion can also be triggered in cells transformed by oncogenes, suggesting it may be a mechanism through which tumor cells escape their microenvironment. In previous work, we demonstrated that p60AmotL2 modulates the E-cadherin function by inhibiting its connection to radial actin filaments. This isoform of AmotL2 is expressed in invasive breast and colon tumors and promotes invasion in vitro and in vivo. Transcriptionally regulated by c-Fos, p60AmotL2 is induced by local stress signals such as severe hypoxia. In this study, we investigated the normal role of p60AmotL2 in epithelial tissues. We found that this isoform is predominantly expressed in the gut, where cells experience rapid turnover. Through time-lapse imaging, we present evidence that cells expressing p60AmotL2 are extruded by their normal neighboring cells. Based on these findings, we hypothesize that tumor cells exploit this pathway to detach from normal epithelia and invade surrounding tissues.

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