School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Professor Pakorn (Tony) Kanchanawong, Associate Professor of Department of Biomedical Engineering, Deputy Director & Principal Investigator of Mechanobiology Institute, National University of Singapore
Talk Title: New aspects in mitosis regulation by cadherin cell-cell adhesion receptor

Date: 18 November 2024 (Monday)
Time: 4:00 pm – 5:00 pm
Venue: Lecture Theatre 3, G/F, William M.W. Mong Block, 21 Sassoon Road
Host: Professor Cheng-han Yu

Biography

Professor Tony Kanchanawong is currently serving as the Deputy Director of the Mechanobiology Institute, with a joint appointment at the Department of Biomedical Engineering, National University of Singapore. His current research focuses on: I. the mechanobiology of cell adhesion receptors and its interplay with diverse cellular signalling pathways (Bertocchi et al., Nature Cell Biology 2017; Liu et al., PNAS 2015, Wu et al. Developmental Cell 2015); and II. the development and application of super-resolution and advanced microscopy methods for mechanobiological studies (Jain et al., Nature Protocols 2022; Xia et al., Cell Reports 2019; Kanchanawong et al., Nature 2010). Prior to joining NUS in 2011 as a recipient of the National Research Foundation Fellowship, he received his Ph.D. in Biophysics from Stanford University in 2007, followed by a postdoctoral training at the National Institutes of Health in Bethesda, Maryland, during 2007-2011.

Abstract

In epithelial tissues, cadherin-mediated cell-cell junctions are known to participate in the regulation of mitosis through the regulation of spindle orientation and the control of cell cycle entry. While the contributions of E-cadherin cell-cell adhesion receptors have been extensively documented, diverse types of cadherins are often co-expressed with E-cadherin but their functions are less well understood. We have been particularly interested in P-cadherin, a close homologue of E-cadherin that co-locates on adjacent chromosomal loci.  Intriguingly, while E-cadherin is commonly considered a tumor suppressor, divergent roles for P-cadherin in different types of cancers have been documented but the underlying mechanism remains obscure.  Recently, we identified P-cadherin as playing an essential role as a guarantor of mitotic fidelity, by serving as a primary regulator of spindle-associated F-actin. Loss of P-cadherin resulted in pervasive mitotic spindle defects and chromosome mis-segregation. Using super-resolution microscopy and optimized fixation, we were able to visualize intricate cytoplasmic and spindle-associated actin networks, and found that they were dependent on P-cadherin. Using differential proximity biotinylation proteomics, we have mapped the signalling pathways mediating P-cadherin control of mitosis.  The involvement of endosomal trafficking, Cdc42 small GTPases, and formin actin polymerization on mitotic regulation by P-cadherin will be discussed. Our findings help delineate the molecular pathways by which P-cadherin ensure proper mitosis. This reveals a previously uncharacterized mechanism by which cell-cell junctions regulate mitotic cell division and offer new insights into the distinct involvement of P-cadherin in various cancer contexts.

ALL ARE WELCOME.