TTF-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma

ABSTRACT: Adenocarcinoma is the most common histologic subtype of lung cancer, which is the leading cause of cancer death. We and others previously identified TTF-1, a lineage-specific transcription factor required for branching morphogenesis and physiological lung functions, as a lineage-survival oncogene in lung adenocarcinoma. However, how TTF-1 mediates survival signals remains elusive. Here we show that TTF-1 induces receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn mediates TTF-1 survival signaling in lung adenocarcinoma. Inhibition of ROR1 impaired prosurvival signaling through the PI3K-AKT pathway and induced nuclear accumulation of FOXO1. These were found to be imposed, at least in part, through PTEN inactivation via c-Src, while ROR1 was shown to physically interact wit

ORGANISM(S): Homo sapiens

SUBMITTER: Takashi Takahashi 

PROVIDER: S-ECPF-GEOD-25830 | biostudies-other |

REPOSITORIES: biostudies-other