Role of Focal Adhesion Kinase in the invasive phenotype of small-cell lung cancer
(2020)
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- Abstract
- Small-cell lung cancer (SCLC) is a devastating illness with frequent metastases and poor survival. The molecular steps leading to SCLC development and progression are still poorly understood and this has translated into the absence of effective targeted therapies and a five-year overall survival as low as 5%. Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase localized at sites of focal adhesions and playing an important role in signal transduction pathways initiated by integrins and G-protein-coupled-receptors. It is overexpressed in many cancers and contributes to cancer progression through a central role in cell adhesion, migration, invasion, survival, and growth, which are highly relevant in SCLC, known to be very aggressive. Since FAK has been poorly studied in SCLC, we decided to investigate it at the functional level in this cancer. We found that FAK was strongly expressed and activated in primary SCLC tumors compared to non-small-cell lung cancer and normal lung. Moreover, inhibition of FAK activity in SCLC cell lines where FAK is overexpressed and constitutively activated decreased FAK phosphorylation (Tyr397) and resulted in antitumoral effects. Inhibition of FAK activity significantly decreased cell proliferation, induced cell cycle arrest in G2/M phases, decreased DNA synthesis, increased apoptosis, and decreased motility as well as invasion in SCLC cell lines. Altogether, this work demonstrates that FAK activation plays a key role in the invasive behaviour of SCLC and suggests that FAK-targeted therapeutic strategies should be evaluated in clinical trials with the hope of reducing mortality from SCLC.
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Aboubakar Nana, F. (2020). Role of Focal Adhesion Kinase in the invasive phenotype of small-cell lung cancer. https://hdl.handle.net/2078.5/167599