Oncostatin M orchestrates collective epithelial migration via HIF1A activation

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• Extracellular signals regulate cell behavior, but mechanisms of ligand-mediated phenotype changes are unclear.
• Oncostatin M (OSM) is a cytokine involved in homeostasis, wound healing, inflammation, and cancer.
• OSM induces collective cell migration (CCM) in mammary epithelial cells.

Purpose of the Study:

• Investigate how OSM drives CCM by comparing it with EGF and IFNG.
• Define ligand-specific phenotypes and molecular networks.
• Elucidate the mechanistic link between OSM signaling, HIF1A, and CCM.

Main Methods:

• Integrative transcriptomic and proteomic analyses.
• Functional validation of identified regulators.
• Comparison of OSM, EGF, and IFNG effects on cell migration.

Main Results:

• Hypoxia-inducible factor-1 (HIF1A) and STAT3 are central regulators of OSM responses.
• HIF1A drives transcriptional programs in hypoxia, metabolism, and immunity.
• Complement signaling is a downstream effector of HIF1A, crucial for OSM-induced CCM.

Conclusions:

• OSM signaling activates HIF1A, coordinating transcriptional reprogramming for epithelial cell migration.
• A mechanistic link between OSM, HIF1A, and CCM is established.
• The identified pathway is active in human breast tumors, potentially contributing to metastasis.