Endogenous DDR2 protein expression levels were high in one cell line, PC-1, and immunohistochemistry of lung cancer tissue array showed high levels of DDR2 protein in 29% of lung SQCC patients.
Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer.
Thus, our results suggest that DDR2 regulation by p300 expression and/or c-Myb acetylation upon matrix stiffening may be necessary for regulation of EMT and invasiveness of lung cancer cells.
We show that DDR2 and SRC are binding partners, that SRC activity is tied to DDR2 activation, and that dual inhibition of both DDR2 and SRC leads to enhanced suppression of DDR2 mutated lung cancer cell lines.
Together, these results suggest that DDR2 mutation can drive lung cancer initiation in vivo and provide a novel mouse model for lung cancer therapeutics studies.
These data may help to anticipate mechanisms of resistance that may be identified in upcoming clinical trials of anti-DDR2 therapy in lung cancer and suggest strategies to overcome resistance.