RBMS1 Coordinates with the m⁶A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Metastasis is a primary driver of lung cancer mortality, with limited effective anti-metastatic therapies.
• Non-small cell lung cancer (NSCLC) exhibits significant metastatic potential, necessitating novel therapeutic targets.

Purpose of the Study:

• To investigate the role of RNA-binding protein RBMS1 in NSCLC metastasis.
• To elucidate the molecular mechanism underlying RBMS1-mediated metastasis.
• To evaluate RBMS1 as a therapeutic target for metastatic NSCLC.

Main Methods:

• Investigated RBMS1 expression and its association with lymph node metastasis in NSCLC.
• Performed in vitro assays (cell migration, invasion) and in vivo metastasis models following RBMS1 depletion.
• Utilized co-immunoprecipitation to identify RBMS1 interacting partners and analyzed protein translation.
• Administered RBMS1 inhibitor NTP in a mouse lung metastasis model.
• Conducted correlation studies in patient cohorts.

Main Results:

• RBMS1 expression positively correlates with lymph node metastasis in NSCLC.
• RBMS1 depletion suppresses NSCLC cell migration, invasion, and in vivo metastasis.
• RBMS1 interacts with YTHDF1 to enhance S100P translation, promoting metastasis.
• The RRM2 motif of RBMS1 and YTH domain of YTHDF1 are crucial for their interaction.
• RBMS1 inhibition via NTP attenuates lung metastasis in mice.
• Clinical data supports the association between RBMS1 and NSCLC metastasis.

Conclusions:

• RBMS1 promotes NSCLC metastasis through YTHDF1-mediated S100P translation.
• Targeting RBMS1 with inhibitors like NTP presents a promising therapeutic strategy for metastatic NSCLC.
• RBMS1 is a clinically relevant molecular driver of NSCLC progression and metastasis.