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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
Summary
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.
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