Abstract
Nucleoli are essential for maintaining cell homeostasis as they regulate the formation of ribosomal subunits, fundamental for protein synthesis. Failure of proper ribosomal biogenesis under favorable conditions or cell stress can create an environment that may favor cancer development. The number and size of nucleoli are commonly altered in almost all cancers and can be considered a prognostic factor due to their influence on cell growth. Despite their recognized morphological significance in tumor progression, the involvement of the nucleolus in the acute tolerance to chemotherapy and the incidence of nucleolar changes after treatment remains unclear. Here, we characterized the nucleolar response of glioblastoma cells to acute temozolomide (TMZ) treatment. The stress induced by TMZ led to notable changes in nucleolar morphology, including increased nucleolar area and number, accompanied by a reduction in circularity. Furthermore, the signals of Ki67 and fibrillarin, proteins associated with cell proliferation and nucleolar activity, were boosted in response to treatment. These responses differed from typical nucleolar stress, here induced by actinomycin-D, suggesting that TMZ triggers an alternative nucleolar response to the stress caused by chemotherapy. These findings highlight a connection between nucleoli and chemotherapy response, offering new insights into the potential mechanisms of tolerance that underlay cancer dynamics.