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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is implicated in tumor-cell growth and metastasis.
• ROR1's roles in inhibiting apoptosis, potentiating EGFR signaling, and inducing proliferation are known, but its specific mechanisms in lung adenocarcinoma metastasis remain unclear.

Purpose of the Study:

• To elucidate the roles and mechanisms of ROR1 in lung adenocarcinoma metastasis.
• To investigate ROR1's impact on epithelial-mesenchymal transition (EMT) and key signaling pathways.

Main Methods:

• Utilized four lung adenocarcinoma cell lines (PC9, PC9erlo, NCI-H358, NCI-H1975) with varying erlotinib sensitivities as models.
• Employed siRNA to silence ROR1 expression.
• Assessed changes in E-cadherin and vimentin expression.
• Evaluated cell migration and invasion in vitro.
• Measured the phosphorylation of Akt, mTOR, Raptor, and p70S6K.

Main Results:

• ROR1 was found to promote EMT by increasing E-cadherin and decreasing vimentin expression.
• Silencing ROR1 significantly reduced lung adenocarcinoma cell migration and invasion.
• ROR1 silencing inhibited the phosphorylation of Akt, mTOR, Raptor, and p70S6K across all tested cell lines.

Conclusions:

• ROR1 plays a central role in lung adenocarcinoma progression and metastasis.
• ROR1 mediates its effects through the mTOR signaling pathway.
• ROR1's role in metastasis is independent of EGFR-TKI sensitivity status.