Introduction: Emerging evidence suggests that enhanced ribosome biogenesis, increased size, and quantitative distribution of nucleoli are associated with dysregulated transcription, which in turn drives a cell into aberrant cellular proliferation and malignancy. Nucleolar alterations have been considered a prognostic histological marker for aggressive tumors. More recently, advancements in the understanding of chromatin network (nucleoplasm viscosity) regulated liquid-liquid phase separation mechanism of nucleolus formation and their multifunctional role shed light on other regulatory processes, apart from ribosomal biogenesis of the nucleolus.
Areas covered: Using hepatocellular carcinoma as a model to study the role of nucleoli in tumor progression, we review the potential of nucleolus coalescence in the onset and development of tumors through non-ribosomal biogenesis pathways, thereby providing new avenues for early diagnosis and cancer therapy.
Expert opinion: Molecular-based classifications have failed to identify the nucleolar-based molecular targets that facilitate cell-cycle progression. However, the algorithm-based tumor risk identification with high-resolution medical images suggests prominent nucleoli, karyotheca, and increased nucleus/cytoplasm ratio as largely associated with tumor recurrence. Nonetheless, the role of the non-ribosomal functions of nucleoli in tumorigenesis remains elusive. This clearly indicates the lacunae in the study of the nucleolar proteins pertaining to cancer. [Figure: see text].
Keywords: NORs; Nucleolus; hepatocellular carcinoma; non-canonical nucleolar pathway; nucleolar proteome.