| Title: |
Dysregulated SASS6 expression promotes increased ciliogenesis and cell invasion phenotypes. |
| 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 |
| Contributors: |
Tsalikis, Athanasios; Natrajan, Rachael; Haider, Syed |
| Publisher Information: |
LIFE SCIENCE ALLIANCE LLC |
| Publication Year: |
2026 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
Humans; Cilia; Cell Cycle Proteins; Transcription Factors; Cell Line; Tumor; Neoplasm Invasiveness; Phenotype; Gene Expression Regulation; Neoplastic; YAP-Signaling Proteins; Adaptor Proteins; Signal Transducing; Lung Neoplasms; Tumor Suppressor Proteins; Signal Transduction; Cell Movement; Centrioles |
| Subject Geographic: |
United States |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Electronic-Print; application/pdf |
| Language: |
English |
| ISSN: |
2575-1077 |
| Relation: |
ARTN e202402820; 8/10/e202402820; Life Science Alliance, 2025, 8 (10), pp. e202402820 -; https://repository.icr.ac.uk/handle/internal/7301 |
| DOI: |
10.26508/lsa.202402820 |
| Availability: |
https://doi.org/10.26508/lsa.202402820; https://repository.icr.ac.uk/handle/internal/7301 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.A08E91F4 |
| Database: |
BASE |