Control of long-distance cell-to-cell communication and autophagosome transfer in squamous cell carcinoma via tunneling nanotubes
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Inés Sáenz-de-Santa-María1, Cristóbal Bernardo-Castiñeira1, Eduardo Enciso2, Inmaculada García-Moreno3, Jose Luis Chiara4, Carlos Suarez1, María-Dolores Chiara1
1Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, CIBERONC, Universidad de Oviedo, Oviedo, Spain
2Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain
3Instituto Química-Física “Rocasolano”, IQFR-CSIC, Madrid, Spain
4Instituto de Química Orgánica General, IQOG-CSIC, Madrid, Spain
María-Dolores Chiara, email: [email protected]
Keywords: tunneling nanotubes, cell communication, FAK, MMP-2, squamous cell carcinomas
Received: July 04, 2016 Accepted: February 06, 2017 Published: February 18, 2017
Tunneling nanotubes (TnTs) are thin channels that temporally connect nearby cells allowing the cell-to-cell trafficking of biomolecules and organelles. The presence or absence of TnTs in human neoplasms and the mechanisms of TnT assembly remains largely unexplored. In this study, we have identified TnTs in tumor cells derived from squamous cell carcinomas (SCC) cultured under bi-dimensional and tri-dimensional conditions and also in human SCC tissues. Our study demonstrates that TnTs are not specific of epithelial or mesenchymal phenotypes and allow the trafficking of endosomal/lysosomal vesicles, mitochondria, and autophagosomes between both types of cells. We have identified focal adhesion kinase (FAK) as a key molecule required for TnT assembly via a mechanism involving the MMP-2 metalloprotease. We have also found that the FAK inhibitor PF-562271, which is currently in clinical development for cancer treatment, impairs TnT formation. Finally, FAK-deficient cells transfer lysosomes/autophagosomes to FAK-proficient cells via TnTs which may represent a novel mechanism to adapt to the stress elicited by impaired FAK signaling. Collectively, our results strongly suggest a link between FAK, MMP-2, and TnT, and unveil new vulnerabilities that can be exploited to efficiently eradicate cancer cells.
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