Dysregulated SASS6 expression promotes increased ciliogenesis and cell invasion phenotypes.
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ICR Authors
Authors
Hargreaves, E
Collinson, R
Jenks, AD
Staszewski, A
Tsalikis, A
Bodoque, R
Arias-Garcia, M
Abdi, Y
Al-Malki, A
Yuan, Y
Natrajan, R
Haider, S
Iskratsch, T
Wang, W-J
Godinho, S
Palaskas, NJ
Calvo, F
Vivanco, I
Zech, T
Tanos, BE
Collinson, R
Jenks, AD
Staszewski, A
Tsalikis, A
Bodoque, R
Arias-Garcia, M
Abdi, Y
Al-Malki, A
Yuan, Y
Natrajan, R
Haider, S
Iskratsch, T
Wang, W-J
Godinho, S
Palaskas, NJ
Calvo, F
Vivanco, I
Zech, T
Tanos, BE
Document Type
Journal Article
Date
2025-08-18
Date Accepted
2025-07-23
Abstract
Centriole and/or cilium defects are characteristic of cancer cells and have been linked to cancer cell invasion. However, the mechanistic bases of this regulation remain incompletely understood. Spindle assembly abnormal protein 6 homolog (SAS-6) is essential for centriole biogenesis and cilium formation. SAS-6 levels decrease at the end of mitosis and G1, resulting from APCCdh1-targeted degradation. To examine the biological consequences of unrestrained SAS-6 expression, we used a nondegradable SAS-6 mutant (SAS-6ND). This led to an increase in ciliation and cell invasion and caused an up-regulation of the YAP/TAZ pathway. SAS-6ND expression resulted in cell morphology changes, nuclear deformation, and YAP translocation to the nucleus, resulting in increased TEAD-dependent transcription. SAS-6-mediated invasion was prevented by YAP down-regulation or by blocking ciliogenesis. Similarly, down-regulation of SAS-6 in DMS273, a highly invasive and highly ciliated lung cancer cell line that overexpresses SAS-6, completely blocked cell invasion and depleted YAP protein levels. Thus, our data provide evidence for a defined role of SAS-6 in cell invasion through the activation of the YAP/TAZ pathway.
Citation
Life Science Alliance, 2025, 8 (10), pp. e202402820 -
Source Title
Life Science Alliance
Publisher
LIFE SCIENCE ALLIANCE LLC
ISSN
2575-1077
eISSN
2575-1077
Collections
Research Team
Signalling Cancer Metab
Functional Genomics
BCR Data Science
Functional Genomics
BCR Data Science