SAS-6 coordinates cell-matrix and cell-cell interactions to promote cancer cell migration

Background The ability of cancer cells to migrate is essential for metastatic progression. Centrioles regulate cytoskeleton remodelling and cell polarity, two key stages of migration, whilst centrosome amplification is commonly observed in aggressive cancer types. Spindle assembly abnormal protein 6 homolog (SAS-6) is a central component of centrioles required for normal duplication and function. To understand further how centrioles could affect cell migration, here we investigated the effects of depleting and overexpressing SAS-6 on cell morphology and movement in physiologically relevant cell derived matrices (CDMs). Methods SAS-6 levels were depleted in a metastatic small cell lung cancer cell line using shRNA-mediated gene knockdown. The effects of overexpression of a non-degradable form of SAS-6 were also investigated. The biological significance of SAS-6 perturbation on cell migration was investigated using live cell imaging. Actin organisation, cell junction formation, and cell membrane dynamics were analysed using immunofluorescence and open-source computational software. Results A metastatic small cell lung cancer cell line was characterised upon SAS-6 depletion, which was found to reduce centriole amplification and cilia number. Depletion of SAS-6 reduced cell migration in CDMs, whilst SAS-6 overexpression increased migration speed and distance. SAS-6 depletion increased focal adhesion number and size, altered actin organisation, disrupted cell anterior-posterior polarity, and weakened cell-cell contacts. Conclusions This study shows a role for the centriolar protein SAS-6 in the regulation of cell migration, likely through coordinating cellular interactions with the surrounding matrix and neighbouring cells, as well as regulating anterior-posterior polarity during cell movement. These observations provide strong rationale to explore SAS-6 as a therapeutic target in cancer metastasis.