Modulation of E-Cadherin Function through the AmotL2 Isoforms Promotes Ameboid Cell Invasion.

Autor: Subramani A; Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden., Cui W; Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden., Zhang Y; Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden., Friman T; Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden., Zhao Z; Department of Physics, Faculty of Science: 2 Science Drive 3, S7-01-10, Lower Kent Ridge Road, Singapore 117542, Singapore.; Mechanobiology Institute (MBI): T-Lab, #10-02, 5A Engineering Drive 1, National University of Singapore, Singapore 117411, Singapore., Huang W; Department of Physics, Faculty of Science: 2 Science Drive 3, S7-01-10, Lower Kent Ridge Road, Singapore 117542, Singapore.; Mechanobiology Institute (MBI): T-Lab, #10-02, 5A Engineering Drive 1, National University of Singapore, Singapore 117411, Singapore., Fonseca P; Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden., Lui WO; Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden., Narayanan V; Department of Biomedical Engineering, Virginia Commonwealth University, 401 West Main Street, Richmond, VA 23284, USA., Bobrowska J; Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow, Poland., Lekka M; Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow, Poland., Yan J; Department of Physics, Faculty of Science: 2 Science Drive 3, S7-01-10, Lower Kent Ridge Road, Singapore 117542, Singapore.; Mechanobiology Institute (MBI): T-Lab, #10-02, 5A Engineering Drive 1, National University of Singapore, Singapore 117411, Singapore., Conway DE; Department of Biomedical Engineering, Virginia Commonwealth University, 401 West Main Street, Richmond, VA 23284, USA., Holmgren L; Department of Oncology and Pathology, U2, Bioclinicum J6:20, Solnavägen 30 Karolinska Institutet, Solna, 171 64 Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 Jun 21; Vol. 12 (13). Date of Electronic Publication: 2023 Jun 21.
DOI: 10.3390/cells12131682
Abstrakt: The spread of tumor cells and the formation of distant metastasis remain the main causes of mortality in cancer patients. However, the mechanisms governing the release of cells from micro-environmental constraints remain unclear. E-cadherin negatively controls the invasion of epithelial cells by maintaining cell-cell contacts. Furthermore, the inactivation of E-cadherin triggers invasion in vitro. However, the role of E-cadherin is complex, as metastasizing cells maintain E-cadherin expression, which appears to have a positive role in the survival of tumor cells. In this report, we present a novel mechanism delineating how E-cadherin function is modulated to promote invasion. We have previously shown that E-cadherin is associated with p100AmotL2, which is required for radial actin formation and the transmission of mechanical force. Here, we present evidence that p60AmotL2, which is expressed in invading tumor cells, binds to the p100AmotL2 isoform and uncouples the mechanical constraint of radial actin filaments. We show for the first time that the coupling of E-cadherin to the actin cytoskeleton via p100AmotL2 is directly connected to the nuclear membrane. The expression of p60AmotL2 inactivates this connection and alters the properties of the nuclear lamina, potentiating the invasion of cells into micropores of the extracellular matrix. In summary, we propose that the balance of the two AmotL2 isoforms is important in the modulation of E-cadherin function and that an imbalance of this axis promotes ameboid cell invasion.
Databáze: MEDLINE
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