Dysregulated SASS6 Expression Promotes Increased Ciliogenesis and Cell Invasion Phenotypes

Authors

Eleanor Hargreaves
Rebecca Collinson
Andrew D Jenks
Adina Staszewski
Athanasios Tsalikis
Raquel Bodoque
Mar Arias-Garcia
Yasmin Abdi
Abdulaziz Al-Malki
Yinyin Yuan
Rachael Natrajan
Syed Haider
Thomas Iskratsch
Won-Jing Wang
Susana Godinho
Nicolaos J Palaskas
Fernando Calvo
Igor Vivanco
Tobias Zech
Barbara E Tanos

Publication Date

10-1-2025

Journal

Life Science Alliance

DOI

10.26508/lsa.202402820

PMID

40825584

PMCID

PMC12361644

PubMedCentral® Posted Date

8-18-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

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

Published Open-Access

yes

Recommended Citation

Hargreaves, Eleanor; Collinson, Rebecca; Jenks, Andrew D; et al., "Dysregulated SASS6 Expression Promotes Increased Ciliogenesis and Cell Invasion Phenotypes" (2025). Faculty, Staff and Student Publications. 5180.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5180