Revisiting the Concept of Stress in the Prognosis of Solid Tumors: A Role for Stress Granules Proteins?

Aulas, Anaïs; Finetti, Pascal; Lyons, Shawn M.; Bertucci, François; Birnbaum, Daniel; Acquaviva, Claire; Mamessier, Émilie

doi:10.3390/cancers12092470

Cited by 19 publications

(22 citation statements)

References 163 publications

(269 reference statements)

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“…colon cancer has been shown to exert the opposite effects by enhancing tumor growth, angiogenesis, and chemoresistance, adding complexity to the participation of SG proteins in cancer (Hamdollah Zadeh et al, 2015;Aulas et al, 2020). G3BP1, another RBP critical for SG assembly, has been shown to promote tumor progression, metastasis, cell proliferation, and chemoresistance (Dou et al, 2016;Wang Y. et al, 2018;Zhang Q. et al, 2019;Zhang C. H. et al, 2021;Zhao et al, 2021).…”

Section: Cancermentioning

confidence: 99%

“…Extensive reviews have been published regarding the links that exist between SGs and cancer ( El-Naggar and Sorensen, 2018 ; Gao et al, 2019 ; Spannl et al, 2019 ; Verdile et al, 2019 ; Aulas et al, 2020 ). In brief, first, SG components are involved in carcinogenesis and cancer metastasis.…”

Section: Stress Granules As Therapeutic Targets In Rna Virus Infection Cancer and Neurodegenerationmentioning

confidence: 99%

“…For example, the reduction in TIA-1 and TIAR has been shown to trigger cell proliferation and tumor growth and accelerate mitotic entry, respectively ( Sanchez-Jimenez et al, 2015 ; Lafarga et al, 2019 ). However, a short splicing variant of TIA-1 expressed in human colon cancer has been shown to exert the opposite effects by enhancing tumor growth, angiogenesis, and chemoresistance, adding complexity to the participation of SG proteins in cancer ( Hamdollah Zadeh et al, 2015 ; Aulas et al, 2020 ). G3BP1, another RBP critical for SG assembly, has been shown to promote tumor progression, metastasis, cell proliferation, and chemoresistance ( Dou et al, 2016 ; Wang Y. et al, 2018 ; Zhang Q. et al, 2019 ; Zhang C. H. et al, 2021 ; Zhao et al, 2021 ).…”

Section: Stress Granules As Therapeutic Targets In Rna Virus Infection Cancer and Neurodegenerationmentioning

confidence: 99%

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The Integral Role of RNA in Stress Granule Formation and Function

Campos-Melo

Hawley

Droppelmann

et al. 2021

Front. Cell Dev. Biol.

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Stress granules (SGs) are phase-separated, membraneless, cytoplasmic ribonucleoprotein (RNP) assemblies whose primary function is to promote cell survival by condensing translationally stalled mRNAs, ribosomal components, translation initiation factors, and RNA-binding proteins (RBPs). While the protein composition and the function of proteins in the compartmentalization and the dynamics of assembly and disassembly of SGs has been a matter of study for several years, the role of RNA in these structures had remained largely unknown. RNA species are, however, not passive members of RNA granules in that RNA by itself can form homo and heterotypic interactions with other RNA molecules leading to phase separation and nucleation of RNA granules. RNA can also function as molecular scaffolds recruiting multivalent RBPs and their interactors to form higher-order structures. With the development of SG purification techniques coupled to RNA-seq, the transcriptomic landscape of SGs is becoming increasingly understood, revealing the enormous potential of RNA to guide the assembly and disassembly of these transient organelles. SGs are not only formed under acute stress conditions but also in response to different diseases such as viral infections, cancer, and neurodegeneration. Importantly, these granules are increasingly being recognized as potential precursors of pathological aggregates in neurodegenerative diseases. In this review, we examine the current evidence in support of RNA playing a significant role in the formation of SGs and explore the concept of SGs as therapeutic targets.

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Section: Cancermentioning

confidence: 99%

Section: Stress Granules As Therapeutic Targets In Rna Virus Infection Cancer and Neurodegenerationmentioning

confidence: 99%

Section: Stress Granules As Therapeutic Targets In Rna Virus Infection Cancer and Neurodegenerationmentioning

confidence: 99%

See 1 more Smart Citation

The Integral Role of RNA in Stress Granule Formation and Function

Campos-Melo

Hawley

Droppelmann

et al. 2021

Front. Cell Dev. Biol.

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“…3E-F). The protein composition of SGs may also be important in predicting the aggressiveness of cancer in patients [40].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of translation inhibition and suppression of Stress Granule formation by cisplatin

Pietras¹,

Aulas

Fay

et al. 2021

Preprint

Self Cite

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Platinum-based antineoplastic drugs, such as cisplatin, are commonly used to induce tumor cell death. Cisplatin is believed to induce apoptosis as a result of cisplatin-DNA adducts that inhibit DNA and RNA synthesis. Although idea that DNA damage underlines anti-proliferative effects of cisplatin is dominant in cancer research, there is a poor correlation between the degree of the cell sensitivity to cisplatin and the extent of DNA platination. Here, we propose a novel mechanism of cisplatin-mediated cytotoxicity. We show that cisplatin suppresses formation of Stress Granules (SGs), pro-survival RNA granules with multiple roles in cellular metabolism. Mechanistically, cisplatin inhibits cellular translation to promote disassembly of polysomes and aggregation of ribosomal subunits. As SGs are in equilibrium with polysomes, cisplatin-induced shift towards ribosomal aggregation suppresses SG formation and promotes cellular death. Our data also explain nephrotoxic, neurotoxic and ototoxic effects of cisplatin treatment.

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“…Tumor formation and progression encompass sequential cellular events that all involve RNP granules [30] (Figure 2). Remarkably, elevated expression of SG markers has been reported in various types of human cancers and predicts a poor prognosis [44].…”

Section: Rnp Granules In Tumorigenesis and Metastasismentioning

confidence: 99%

Cancer cell adaptability: turning ribonucleoprotein granules into targets

et al. 2021

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Stress granules (SGs) and processing bodies (P-bodies) are membraneless cytoplasmic condensates of ribonucleoproteins (RNPs). They both regulate RNA fate under physiological and pathological conditions, and are thereby involved in the regulation and maintenance of cellular integrity. During tumorigenesis, cancer cells use these granules to thrive, to adapt to the harsh conditions of the tumor microenvironment (TME), and to protect themselves from anticancer treatments. This ability to provide multiple outcomes not only makes RNP granules promising targets for cancer therapy but also emphasizes the need for more knowledge about the biology of these granules to achieve clinical use. In this review we focus on the role of RNP granules in cancer, and on how their composition and regulation might be used to elaborate therapeutic strategies. RNP granules between stress and translationRegulating the expression of the genomic information is crucial to ensure cell identity and functionality. During transformation into cancer cells and throughout tumor progression, cells dynamically modulate the expression of their genomic information to adapt to environmental cues. Control of mRNA translation ensures the spatiotemporal adjustment of protein synthesis, and is often dysregulated in cancer cells to favor their adaptability [1]. In particular, regulation of translation initiation allows cancer cells to reprogram this activity towards essential mRNAs, such as those encoding oncogenes, to facilitate cell growth, proliferation, and survival [2]. Moreover, cancer cells must adapt to stress conditions in the TME, mainly through activation of the integrated stress response (ISR) [3,4] (Figure 1). This pathway controls translation initiation through eukaryotic initiation factor 2 (eIF2), which, once phosphorylated on its α subunit, prevents the formation of the ternary complex (eIF2:GTP: methionyl-initiator-tRNA) and consequently blocks translation initiation [5]. Four stress-sensor kinases can induce eIF2α phosphorylation, namely the PKR-like endoplasmic reticulum kinase (PERK), general control nonrepressible 2 (GCN2), heme-regulated inhibitor (HRI), and protein kinase R (PKR). The outcome of ISR activation is a global decrease in protein synthesis, while sparing the translation of some specific mRNAs such as that of transcription factor ATF4 [4]. Activation of this pathway, and the resulting selective translation, favor tumor progression following endoplasmic reticulum stress caused for instance by the hypoxic TME [6]. Furthermore, ISR activation by aberrant MYC expression enables cancer cells to adapt to this intrinsic stress by reprogramming translational programs. Consequently, the ISR prevents cancer cells from entering apoptosis and promotes both tumor progression [7,8] and escape from antitumor immunity [9,10].

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Revisiting the Concept of Stress in the Prognosis of Solid Tumors: A Role for Stress Granules Proteins?

Cited by 19 publications

References 163 publications

The Integral Role of RNA in Stress Granule Formation and Function

The Integral Role of RNA in Stress Granule Formation and Function

Mechanisms of translation inhibition and suppression of Stress Granule formation by cisplatin

Cancer cell adaptability: turning ribonucleoprotein granules into targets

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