Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion

Area of Science:

• Cell Biology
• Cancer Research
• Epithelial Biology

Background:

• Centrosome aberrations disrupt tissue organization and can promote cancer invasion.
• Normal epithelial cells remove damaged cells via apical extrusion.
• Oncogenic mutations can shift cell extrusion directionality to the basal side, risking metastasis.

Purpose of the Study:

• To investigate how structural centrosome aberrations affect cell extrusion directionality in polarized mammalian epithelia.
• To understand the role of Ninein-like protein (NLP) and CEP131 in centrosome-mediated cell extrusion.
• To determine the impact of these aberrations on tissue architecture and potential metastatic dissemination.

Main Methods:

• Overexpression of Ninein-like protein (NLP) and CEP131/AZI1 in mammalian epithelial cells.
• Induction of cell damage to observe extrusion.
• Microscopic analysis of microtubule cytoskeleton reorganization and cell extrusion directionality.
• Utilizing MDCK cysts to model epithelial tissue.

Main Results:

• NLP-induced centrosome aberrations preferentially direct damaged cells towards basal extrusion.
• Microtubule cytoskeleton reorganization prevents apical extrusion by inhibiting contractile ring repositioning.
• CEP131 overexpression induces spontaneous basal dissemination of dying cells from MDCK cysts.
• Structural centrosome aberrations mimic oncogenic mutations in favoring basal cell extrusion.

Conclusions:

• Structural centrosome aberrations can reprogram polarized epithelia to extrude damaged cells basally.
• This basal extrusion mechanism, similar to oncogenic processes, may facilitate metastatic spread.
• Further mutations promoting cell survival could enhance the metastatic potential of epithelia with centrosome aberrations.