Phosphorylation of interleukin (IL)-24 is required for mediating its anti-cancer activity

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Interleukin-24 (IL-24) is a cytokine with tumor suppressor functions.
• Post-translational modifications (PTMs) like glycosylation and ubiquitination affect IL-24 stability and degradation.
• The role of IL-24 phosphorylation in its anti-tumor activity remains largely unexplored.

Purpose of the Study:

• To investigate the significance of IL-24 phosphorylation in mediating anti-cancer activities.
• To elucidate the molecular mechanisms underlying IL-24's anti-tumor effects, specifically focusing on the AKT/mTOR pathway.

Main Methods:

• Utilized a doxycycline-inducible system in H1299 lung tumor cells expressing either wild-type IL-24 (IL-24wt) or a phosphorylation-deficient mutant (IL-24mt).
• Assessed tumor cell proliferation, migration, invasion, and cell cycle progression.
• Analyzed protein secretion, subcellular localization, and the AKT/mTOR signaling pathway activity.

Main Results:

• IL-24wt expression inhibited tumor cell proliferation, migration, invasion, and induced G2/M cell cycle arrest, while IL-24mt did not.
• IL-24mt exhibited reduced secretion and altered subcellular localization compared to IL-24wt.
• IL-24wt, but not IL-24mt, inhibited the AKT/mTOR signaling pathway, a finding confirmed by siRNA-mediated AKT knockdown and AKT overexpression studies.

Conclusions:

• IL-24 phosphorylation is essential for its anti-cancer properties.
• Phosphorylation enables IL-24 to inhibit the AKT/mTOR signaling pathway, thereby exerting its tumor-suppressive functions.