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SUMMARY:Cytoskeleton club Anita Baillet "Septin subcellular partitioning a
 t the core of the mechanobiological stress response in cancer"
DTSTART:20260612T090000Z
DTEND:20260612T110000Z
DTSTAMP:20260513T200700Z
UID:indico-event-383@indico.i2bc.paris-saclay.fr
DESCRIPTION:Speaker: Anita Baillet - INSERM UMR-S 1193\, UFR de Pharmacie\
 , Université Paris-Saclay\, Orsay\n\n \n \n \n \n \n \n \n \nTitl
 e: Septin subcellular partitioning at the core of the mechanobiological st
 ress response in cancer\nAbstract: \nMaintenance of cellular mechanical h
 omeostasis is crucial for proper cell functions but can be challenged by i
 nternal or external stress factors\, including therapy and mechanic stress
 es related to the tumor environment. \n \nBy investigating cytoskeleton-
 mediated cell adaptation to stress\, we previously evidenced a novel mecha
 nism of taxane resistance in breast cancer cells that involves the overexp
 ression of septins\, a family of cytoskeleton proteins. Taxanes early make
 s septins to relocalize from actin stress fibers to microtubules (MTs)\, c
 ounteracting its MT-stabilizing effect and promoting chemoresistance. Inte
 restingly\, this fast relocalization was also observed when cells are grow
 n on low-stiffness extracellular matrix (ECM) or overloaded with cytoplasm
 ic lipid droplets. In all stress conditions\, the cytoskeleton remodeling 
 is paralleled by a loss and thinning of actin stress fibers and correlates
  with mechanotransduction abnormalities\, altering the transmission of the
  stress signal to the nucleus.\n \nFocal adhesions are less abundant\, an
 d nuclear YAP translocation is substantially inhibited. Using Atomic Force
  Microscopy\, we further observed a decrease in cell elasticity\, which ma
 y result from reorganization of the subcortical actin network. Finally\, t
 hrough analyses of cell shape on micropatterns and Traction Force Microsco
 py experiments\, we demonstrated a decrease in stress fiber tension and ce
 llular contractility. Furthermore\, a common transcriptomic signature asso
 ciated with septin relocalization-mediated alterations in mechanotransduct
 ion was identified\, highlighting a set of seven genes that were early upr
 egulated both after 24h of Taxol® treatment and during cell culture on a 
 soft matrix. The most significant hits are involved in regulating gene exp
 ression (EHF\, LINC01348…)\, cell signaling and plasticity (ABCA1\, SERP
 INB4\, ARRDC3…)\, and in the secretion of indirect modifiers of the ECM 
 (AREG\, TNFAIP6…).\n \nOverall\, this septin relocalization stress resp
 onse could appear as a general early adaptation mechanism to mechanical st
 ress and might open new therapeutic strategies to limit tumor initiation\,
  progression\, and chemoresistance.\n \n\nInvited by Arthur Molines\n \
 n\nhttps://indico.i2bc.paris-saclay.fr/event/383/
LOCATION:B24-N2-315 (I2BC CNRS Gif)
URL:https://indico.i2bc.paris-saclay.fr/event/383/
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