The effects of verteporfin on non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers and is the leading cause of cancer death in the Unites States. Better treatments must be devised in order to improve the prognosis of this disease. Verteporfin, an FDA approved drug, has recently been reported to downregulate a potential core pathway of NSCLC, the Hippo pathway. The pathway consists of a kinase cascade to control the transcriptional coactivators YAP and TAZ. When these transcriptional coactivators lack phosphorylation of key residues, they are able to translocate into the nucleus and bind to the TEAD member of transcription factors. This augments transcription for genes responsible for proliferation, survival, and stem maintenance. In this study, we report that verteporfin limits proliferation and survival of NSCLC and may potentially be a viable treatment option. Inhibition of cell survival dose-dependently correlated with inhibition of YAP-TEAD transcription target CTGF. We also report the covalent homo-oligomerization of p62, a prominent protein involved with autophagy, with the introduction of verteporfin into NSCLC cells.