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Induction and Analysis of Epithelial to Mesenchymal Transition
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Modulation of E-Cadherin Function through the AmotL2 Isoforms Promotes Ameboid Cell Invasion

Aravindh Subramani1, Weiyingqi Cui1, Yuanyuan Zhang1

  • 1Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden.

Cells
|July 14, 2023
PubMed

Insights

Tumor cell invasion and metastasis are key cancer mortality factors. A novel mechanism reveals how E-cadherin and AmotL2 isoforms control cell release and invasion, impacting cancer progression.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Metastasis is a primary cause of cancer patient mortality.
  • Mechanisms of tumor cell release from micro-environmental constraints are not fully understood.
  • E-cadherin, crucial for cell-cell adhesion, has a complex role in invasion and survival.

Purpose of the Study:

  • To elucidate a novel mechanism of E-cadherin modulation promoting cancer cell invasion.
  • To investigate the role of AmotL2 isoforms in regulating E-cadherin function and cell motility.
  • To understand how E-cadherin-cytoskeleton-nucleus connections influence tumor cell invasion.

Main Methods:

  • Investigated the association between E-cadherin and p100/p60AmotL2 isoforms.
  • Analyzed the effect of p60AmotL2 on radial actin formation and mechanical force transmission.
  • Examined the connection between E-cadherin, actin cytoskeleton, and the nuclear membrane.
  • Assessed changes in nuclear lamina properties and cell invasion through micropores.

Main Results:

  • p60AmotL2 binds to p100AmotL2, uncoupling radial actin filaments and E-cadherin.
  • E-cadherin coupling to the actin cytoskeleton via p100AmotL2 connects to the nuclear membrane.
  • p60AmotL2 expression disrupts this connection, altering nuclear lamina properties.
  • This disruption potentiates cell invasion into the extracellular matrix.

Conclusions:

  • The balance between p100AmotL2 and p60AmotL2 isoforms is critical for modulating E-cadherin function.
  • An imbalance in AmotL2 isoforms promotes ameboid cell invasion.
  • This axis represents a potential therapeutic target for inhibiting cancer metastasis.
Keywords:
AmotL2E-cadherinactincancercancer invasionmechanotransductionmetastasisnuclear laminap60AmotL2

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