Journal
ONCOTARGET
Volume 8, Issue 13, Pages 20939-20960Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15467
Keywords
tunneling nanotubes; cell communication; FAK; MMP-2; squamous cell carcinomas
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Funding
- Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria [FIS PI11/929]
- Red Tematica de Investigacion Cooperativa en Cancer, CIBERONC, Instituto de Salud Carlos III (ISCIII) Spanish Ministerio de Economia y Competitividad & European Regional Development Fund (ERDF) [RD12/0036/0015]
- Spanish Ministerio de Economia y Competitividad [MAT2014-51937-C3-1-P, MAT2015-68837-REDT]
- Fundacion Bancaria Caja de Ahorros de Asturias-Instituto Universitario de Oncologia del Principado de Asturias
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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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