The nucleolus: a central response hub for the stressors that drive cancer progression

Weeks, Shannon E.; Metge, Brandon J.; Samant, Rajeev S.

doi:10.1007/s00018-019-03231-0

Cited by 98 publications

(96 citation statements)

References 148 publications

(160 reference statements)

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“…Nucleolus, the site of ribosome biogenesis, is recently considered as central hub in the cellular stress response [29,30]. Nucleolus can favor neoplasia since many proteins which are related to ribosome production as r-proteins perform non-ribosomal functions and can be engaged in malignancy, including transformation, cancer development and drug resistance [31].…”

Section: Discussionmentioning

confidence: 99%

Role of uL3 in the Crosstalk between Nucleolar Stress and Autophagy in Colon Cancer Cells

Pecoraro

Carotenuto

Bazzoli

et al. 2020

IJMS

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The nucleolus is the site of ribosome biogenesis and has been recently described as important sensor for a variety of cellular stressors. In the last two decades, it has been largely demonstrated that many chemotherapeutics act by inhibiting early or late rRNA processing steps with consequent alteration of ribosome biogenesis and activation of nucleolar stress response. The overall result is cell cycle arrest and/or apoptotic cell death of cancer cells. Our previously data demonstrated that ribosomal protein uL3 is a key sensor of nucleolar stress activated by common chemotherapeutic agents in cancer cells lacking p53. We have also demonstrated that uL3 status is associated to chemoresistance; down-regulation of uL3 makes some chemotherapeutic drugs ineffective. Here, we demonstrate that in colon cancer cells, the uL3 status affects rRNA synthesis and processing with consequent activation of uL3-mediated nucleolar stress pathway. Transcriptome analysis of HCT 116p53−/− cells expressing uL3 and of a cell sub line stably depleted of uL3 treated with Actinomycin D suggests a new extra-ribosomal role of uL3 in the regulation of autophagic process. By using confocal microscopy and Western blotting experiments, we demonstrated that uL3 acts as inhibitory factor of autophagic process; the absence of uL3 is associated to increase of autophagic flux and to chemoresistance. Furthermore, experiments conducted in presence of chloroquine, a known inhibitor of autophagy, indicate a role of uL3 in chloroquine-mediated inhibition of autophagy. On the basis of these results and our previous findings, we hypothesize that the absence of uL3 in cancer cells might inhibit cancer cell response to drug treatment through the activation of cytoprotective autophagy. The restoration of uL3 could enhance the activity of many drugs thanks to its pro-apoptotic and anti-autophagic activity.

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Section: Discussionmentioning

confidence: 99%

Role of uL3 in the Crosstalk between Nucleolar Stress and Autophagy in Colon Cancer Cells

Pecoraro

Carotenuto

Bazzoli

et al. 2020

IJMS

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“…The first link between nucleoli and cancer was established over a century ago, when pathologists noticed that nucleoli in cancer cells are often enlarged, irregularly shaped, as well as increased in number and therefore could serve as markers of aggressive malignancies [156]. In general, the roles of nucleolar processes in cancer biology are manifold and for a more in-depth discussion on this topic the reader is referred to comprehensive recent review articles [6,17,29,30,157]. Broadly speaking, the role of nucleoli in carcinogenesis falls into two interdependent categories: ribosome biogenesis and stress response.…”

Section: Implications For Cancer Biologymentioning

confidence: 99%

“…Nucleolar size positively correlates with rRNA synthesis and cell proliferation, as dividing cells often possess large nucleoli, while downregulation of rRNA gene transcription is associated with a reduction in nucleolar size [2]. Interestingly, an increased number and size of nucleoli have historically been used as a biomarker for tumor development [6].…”

Section: Introduction Into the Biology Of Nucleolimentioning

confidence: 99%

The Nucleolus and PARP1 in Cancer Biology

Engbrecht¹,

Mangerich²

2020

Cancers

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The nucleolus has been known for a long time to fulfill crucial functions in ribosome biogenesis, of which cancer cells can become addicted to in order to produce sufficient amounts of proteins for cell proliferation. Recently, the nucleolus has emerged as a central regulatory hub in many other cancer-relevant processes, including stress sensing, DNA damage response, cell cycle control, and proteostasis. This fostered the idea that nucleolar processes can be exploited in cancer therapy. Interestingly, a significant proportion of poly(ADP-ribose) polymerase 1 (PARP1) molecules are localized in the nucleolus and PARP1 also plays crucial roles in many processes that are important in cancer biology, including genome maintenance, replication, transcription, and chromatin remodeling. Furthermore, during the last years, PARP1 came into focus in oncology since it represents a promising target of pharmacological PARP inhibitors in various types of cancers. Here, we provide an overview of our current understanding on the role of PARP1 in nucleolar functions and discuss potential implications in cancer biology and therapy.

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“…Michael White (Richard Kriwacki's laboratory, St. Jude Children's Research Hospital) used biophysical methods to examine how nucleophosmin's interaction with Arg-rich peptides encoded in C9orf72 hexanucleotide repeat expansion forms and dissolves biomolecular condensates in vitro and nucleoli in cells (10). Shannon Weeks (Rajeev Samant's laboratory, University of Alabama, Birmingham) highlighted the close relationship of nucleolar abnormalities and cancer (11) and reported the effect of inhibition of Wnt signaling in triple-negative breast cancer on the nucleolar proteome, identifying Las1L as a good candidate for targeting the nucleolus in triple-negative breast cancer.…”

Section: Nucleoli Under Stressmentioning

confidence: 99%

Emerging Roles for the Nucleolus 2019

Baserga

Duncan

2020

Journal of Biological Chemistry

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The nucleolus is the central organelle within eukaryotic cells whose primary function is to generate ribosomes, the major protein producing machines within all cells. New roles for the nucleolus are continuously emerging as we explore its molecular intricacies. Despite the central and fundamental role of the nucleolus in cell biology, there has previously been no single official meeting that enables the gathering of scientists whose research converges on the nucleolus. As a result, the community of researchers who study this organelle risks fragmentation across disciplines. The Emerging Roles for the Nucleolus Symposium, which has now taken place twice on a biennial basis, first in 2017 (1) and again in 2019, therefore, represents the first of its kind. The overarching goals of this symposium are (a) to convene researchers who study the nucleolus across model systems (yeast, nematodes, fruit flies, mouse, human cell lines) and biological perspectives (structural, biophysical, molecular, cellular, pathophysiology), (b) to share and disseminate the latest research breakthroughs in nucleolar biology, (c) to promote interaction, engagement, and collaboration centered on the nucleolus across disciplines, and (d) to provide trainees and early career investigators with an organelle-specific scientific community of support.

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The nucleolus: a central response hub for the stressors that drive cancer progression

Cited by 98 publications

References 148 publications

Role of uL3 in the Crosstalk between Nucleolar Stress and Autophagy in Colon Cancer Cells

Role of uL3 in the Crosstalk between Nucleolar Stress and Autophagy in Colon Cancer Cells

The Nucleolus and PARP1 in Cancer Biology

Emerging Roles for the Nucleolus 2019

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