A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Metastasis is a leading cause of cancer mortality, involving complex processes like epithelial-mesenchymal transition (EMT).
• Centrosome abnormalities are linked to tumor aggressiveness, but specific protein roles in metastasis are unclear.

Purpose of the Study:

• To investigate the role of STIL (SCL/TAL1-interrupting locus) protein in cancer progression and metastasis.
• To elucidate the molecular mechanisms underlying STIL's oncogenic functions.

Main Methods:

• In silico analysis of TCGA, GEO, and EBI datasets for centriolar/centrosomal gene expression.
• Immunohistochemistry (IHC) for STIL protein in clinical specimens.
• In vitro and in vivo assays (migration, invasion, xenograft, metastasis) to assess STIL's oncogenic roles.
• RNA-seq, qPCR, reporter assays, and ChIP-qPCR to identify and confirm STIL-mediated pathways.

Main Results:

• STIL expression is significantly increased in lung and other cancers, correlating with poor survival.
• STIL depletion inhibits tumor growth and metastasis; excess STIL activates EMT, enhancing migration and invasion.
• STIL translocates to the nucleus, associating with FOXM1 to promote metastasis and stemness.
• Hypoxia-inducible factor 1α (HIF1α) directly upregulates STIL expression under hypoxia.

Conclusions:

• STIL promotes tumor metastasis via the HIF1α-STIL-FOXM1 signaling axis.
• STIL represents a potential therapeutic target for lung cancer treatment.