Dysregulated <i>SASS6</i> expression promotes increased ciliogenesis and cell invasion phenotypes
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 APC<sup>Cdh1</sup>-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.
Authors
- Eleanor Hargreaves (ORCID: https://orcid.org/0000-0002-9287-8480)
- Igor Vivanco (ORCID: https://orcid.org/0000-0001-6347-9416)
- Yinyin Yuan (ORCID: https://orcid.org/0000-0002-8556-4707)
- Rebecca Collinson
- Tobias Zech (ORCID: https://orcid.org/0000-0001-8394-088X)
- Athanasios Tsalikis (ORCID: https://orcid.org/0000-0003-4994-4312)
- Fernando Calvo (ORCID: https://orcid.org/0000-0001-8858-1185)
- Syed Aleem Haider (ORCID: https://orcid.org/0000-0001-6685-5480)
- Rachael Natrajan (ORCID: https://orcid.org/0000-0002-9987-2946)
- B Tanos (ORCID: https://orcid.org/0000-0002-7045-9496)
- Susana A. Godinho (ORCID: https://orcid.org/0000-0003-0638-065X)
- Mar Arias-García (ORCID: https://orcid.org/0000-0003-0130-1107)
- Nicolaos Palaskas (ORCID: https://orcid.org/0000-0003-0783-0683)
- Won‐Jing Wang (ORCID: https://orcid.org/0000-0001-9733-0839)
- Thomas Iskratsch (ORCID: https://orcid.org/0000-0002-3738-7830)
- Andrew Jenks
- Yasmin Abdi
- Adina Staszewski
- Raquel Bodoque
- Abdulaziz Al-Malki
Institutions
- Universidad de Cantabria (ES)
- The University of Texas MD Anderson Cancer Center (US)
- Consejo Superior de Investigaciones Científicas (ES)
- Institute of Cancer Research (GB)
- University of Liverpool (GB)
- National Yang Ming Chiao Tung University (TW)
- Queen Mary University of London (GB)
- King's College London (GB)
- George Washington University (US)
- Breast Cancer Now (GB)
- University of California System (US)
- Institute of Cancer Research (CA)
- Instituto de Biomedicina y Biotecnología de Cantabria (ES)
- Hospital General Universitario de Ciudad Real (ES)
- Building Research Institute (JP)
- Imperial College London (GB)
- Brunel University of London (GB)
- National Yang Ming Chiao Tung University (TW)
Publication Details
- Journal
- Life Science Alliance
- Published
- 2025-08-18
- DOI
- https://doi.org/10.26508/lsa.202402820
- Primary Topic
- Endoplasmic Reticulum Stress and Disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Johns Hopkins University
- Worldwide Cancer Research
- June Hancock Mesothelioma Research Fund
- Kidney Research UK
- King's College London
- University of Oxford
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- European Research Council
- National Human Genome Research Institute
- National Cancer Institute