Work

The potential role of YAP in Axl-mediated resistance to EGFR tyrosine kinase inhibitors.

Year: 2019

Type: article

Abstract: . Axl overexpression or GAS6 stimulation increased YAP-mediated transcriptional activity, and YAP-mediated colony forming activity in soft agar was enhanced by co-expression of Axl. In EGFR tyrosine kinase inhibitor (TKI)-sensitive lung cancer cells, YAP protein was downregulated in response to TKI treatment, while overexpression of YAP attenuated TKI sensitivity, suggesting that YAP is a key determinant of TKI response. Moreover Axl overexpression reversed TKI-induced YAP downregulation and induced TKI-resistance, which was reversed by YAP knockdown, further supporting the notion that YAP functions downstream of Axl. Together, these findings suggest a novel role of YAP in Axl-mediated TKI resistance.

Source: PubMed Central

Authors: Sarah Saab, Olin Shih-Shin Chang, Kentaro Nagaoka, Mien-Chie Hung, Hirohito Yamaguchi