Prohibitins in cancer: Multifaceted regulators of mitochondrial homeostasis, oncogenic signaling, tumor microenvironment, and therapeutic resistance - PubMed
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- Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are conserved scaffold proteins with roles in cellular physiology.
- They regulate oncogenic pathways like RAS-RAF-MEK-ERK, PI3K/Akt/mTOR, Wnt/β-catenin, and NF-κB.
- PHBs maintain mitochondrial homeostasis, influencing cristae structure, metabolism, and mitophagy.
- They are involved in cell cycle control, stemness, and epigenetic regulation through transcription factors and chromatin modifiers.
- In the tumor microenvironment, PHBs affect immune responses, including macrophage polarization and cGAS-STING activation.
- PHB expression varies by cancer type and impacts prognosis and resistance to therapies like platinum drugs and PARP inhibitors.
- Targeted interventions against PHBs include small molecules, peptides, aptamers, and siRNA platforms for potential clinical use.