Blocking ROR1 enhances the roles of erlotinib in lung adenocarcinoma cell lines.

Treatment strategies involving tyrosine kinase inhibitors (TKIs) for patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations have advanced significantly; however, challenges still remain regarding the development of resistance. It has been reported that receptor tyrosine kinase-like orphan receptor 1 (ROR1) acts as a hepatocyte growth factor receptor (MET) and c-Src substrate, and that the extracellular domain of ROR1 is associated with EGFR to sustain EGFR-ERBB3-PI3K signaling. Our previous study reported that blocking ROR1 significantly decreased the activity of key signal molecules in the AKT/mammalian target of rapamycin (mTOR) signaling pathway, which was associated with a significant increase of apoptosis and significant decrease of proliferation of lung adenocarcinoma cells.

Targeting ROR1 inhibits epithelial to mesenchymal transition in human lung adenocarcinoma via mTOR signaling pathway.

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a type I surface transmembrane protein that contributes to progression of tumor-cell growth and metastasis. We and others have shown that the roles of ROR1 include inhibiting apoptosis, potentiating EGFR signaling, and inducing proliferation in lung cancer, but the roles and mechanisms of ROR1 in lung adenocarcinoma metastasis have not been elucidated. Here we chose four lung adenocarcinoma cell lines, PC9 (erlotinib-sensitive), PC9erlo (acquired erlotinib-resistant), NCI-H358 (partial erlotinib-resistant), and NCI-H1975 (erlotinib-resistant) as cell models to simulate the clinical situation.