Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

23-POS Board 23 Actomyosin Activity is Essential for Contact Inhibition of Keratinocyte Proliferation Hiroaki Hirata 1,2 , Mikhail Samsonov 3 , Masahiro Sokabe 1 . 1 Nagoya University Graduate School of Medicine, Nagoya, Japan, 2 R-Pharm Japan, Tokyo, Japan, 3 R-Pharm, Moscow, Russian Federation. Confluence-dependent inhibition of keratinocyte proliferation, termed contact inhibition, contributes to epidermal homeostasis. Loss of the contact inhibition in keratinocytes is associated with keratinocyte carcinomas, the most common type of cancers in the United States. Whilst both E-cadherin ligation and actomyosin activity have been suggested to regulate proliferation of confluent keratinocytes, it remains elusive how these two cooperate to achieve contact inhibition. Here, we report distinct roles of E-cadherin ligation and actomyosin activity in confluence- dependent regulation of keratinocyte proliferation. Under actomyosin inhibition, cell-cell contact through E-cadherin promoted proliferation of keratinocytes. By contrast, actomyosin activity in confluent keratinocytes inhibited nuclear localization of β-catenin and YAP, and caused attenuation of β-catenin- and YAP-driven cell proliferation. Depending on the actomyosin activity, confluent keratinocytes developed E-cadherin-mediated punctate adhesion complexes, to which radial actin cables were connected, at the apical portions of cell-cell boundaries. Eliminating the actin-to-E-cadherin linkage by depleting α-catenin expression increased proliferation of confluent keratinocytes. External application of pulling force through E-cadherin using magnetic beads, in turn, diminished proliferation of actomyosin-inhibited keratinocytes, suggesting an inhibitory effect of tensile stress at E-cadherin adhesions on keratinocyte proliferation. Our results highlight actomyosin activity as a crucial factor that provokes confluence-dependent inhibition of keratinocyte proliferation.

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