Differential regulation of autophagy by STAU1 in alveolar rhabdomyosarcoma and non‐transformed skeletal muscle cells

Almasi, Shekoufeh; Parks, Tara E. Crawford; Ravel‐Chapuis, Aymeric; MacKenzie, Alex; Côté, Jocelyn; Cowan, Kyle N.; Jasmin, Bernard J.

doi:10.1007/s13402-021-00607-y

Cited by 10 publications

(18 citation statements)

References 79 publications

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“…However, given the heterogeneity and multifactorial nature of cancers, various underlying mechanisms may contribute to the differential functions of STAU1 among cancer types (Fig. 3) [31][32][33].…”

Section: Conclusion and Perspectivementioning

confidence: 99%

“…Based on these observations, STAU1 may thus serve as a potential therapeutic target for the development of novel cancer-specific treatments [31][32][33]. However, the cancerspecific effect of STAU1 targeting needs to be addressed when proposing it as an anti-cancer therapeutic target.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

“…These effects can result from positive or/and negative control of gene expression by STAU1 leading to the inhibition or activation of cell growth. The critical importance of cell growth control mechanisms in cancer progression [ 74 ] accompanied by the observed roles of STAU1 in cell growth, led to recent investigations on the impact of STAU1 on cell growth linked to the pathophysiology and treatment of various cancers [ 18 , 32 , 33 ]. Examination of the STAU1 levels in proliferating human transformed cell lines HCT116 (colon cancer cells) and U2OS (osteosarcoma cells) at different stages of the cell cycle, indicated that STAU1 protein levels increase during the early phases of the cell cycle (S and G2 phases) and rapidly drops later in mitosis.…”

Section: Role Of Stau1 In the Regulation Of Cell Functions And Its Associated Impact On Cancermentioning

confidence: 99%

“…As a result, STAU1’s involvement in cell proliferation [ 18 , 19 ], differentiation [ 20 , 21 ], migration [ 22 ], apoptosis [ 23 ], autophagy [ 24 ], and stress response [ 25 – 27 ] has been uncovered. Given this, dysregulation of STAU1’s expression and/or function has been linked with disrupted cellular functions and with the pathophysiology of several diseases including neurodegenerative [ 24 , 27 , 28 ] and neuromuscular disorders [ 26 , 29 , 30 ], as well as cancer [ 31 – 33 ]. In this review, we focus on the role of STAU1 in cell functions linked to cancer.…”

Section: Introductionmentioning

confidence: 99%

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The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events

Almasi

Jasmin

2021

Cell. Mol. Life Sci.

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The double-stranded multifunctional RNA-binding protein (dsRBP) Staufen was initially discovered in insects as a regulator of mRNA localization. Later, its mammalian orthologs have been described in different organisms, including humans. Two human orthologues of Staufen, named Staufen1 (STAU1) and Staufen2 (STAU2), share some structural and functional similarities. However, given their different spatio-temporal expression patterns, each of these orthologues plays distinct roles in cells. In the current review, we focus on the role of STAU1 in cell functions and cancer development. Since its discovery, STAU1 has mostly been studied for its involvement in various aspects of RNA metabolism. Given the pivotal role of RNA metabolism within cells, recent studies have explored the mechanistic impact of STAU1 in a wide variety of cell functions ranging from cell growth to cell death, as well as in various disease states. In particular, there has been increasing attention on the role of STAU1 in neuromuscular disorders, neurodegeneration, and cancer. Here, we provide an overview of the current knowledge on the role of STAU1 in RNA metabolism and cell functions. We also highlight the link between STAU1-mediated control of cellular functions and cancer development, progression, and treatment. Hence, our review emphasizes the potential of STAU1 as a novel biomarker and therapeutic target for cancer diagnosis and treatment, respectively.

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Section: Conclusion and Perspectivementioning

confidence: 99%

Section: Conclusion and Perspectivementioning

confidence: 99%

Section: Role Of Stau1 In the Regulation Of Cell Functions And Its Associated Impact On Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events

Almasi

Jasmin

2021

Cell. Mol. Life Sci.

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“…In transgenic mice, sustained expression of STAU1 in post-natal skeletal muscle causes a myopathy phenotype by increasing the expression of phosphatase tensin homolog (PTEN) and by inhibiting phosphoinositide-3-kinase (PI3K)/AKT signaling (Crawford Parks et al, 2017). Further overexpression of STAU1 in a mouse model of DM1 exacerbates the myopathy phenotype through a similar mechanism, suggesting that STAU1 is an atrophy-associated gene with impact on progressive muscle wasting in DM1 (Crawford Parks et al, 2020). However, there is also evidence indicating that increased expression of STAU1 may have a beneficial effect on DM1.…”

Section: Stau1 Inhibits Embryonic Myogenesis and Maintains Satellite Cell Quiescencementioning

confidence: 99%

RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

Shi

Grifone

2021

Front. Cell Dev. Biol.

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Embryonic myogenesis is a temporally and spatially regulated process that generates skeletal muscle of the trunk and limbs. During this process, mononucleated myoblasts derived from myogenic progenitor cells within the somites undergo proliferation, migration and differentiation to elongate and fuse into multinucleated functional myofibers. Skeletal muscle is the most abundant tissue of the body and has the remarkable ability to self-repair by re-activating the myogenic program in muscle stem cells, known as satellite cells. Post-transcriptional regulation of gene expression mediated by RNA-binding proteins is critically required for muscle development during embryogenesis and for muscle homeostasis in the adult. Differential subcellular localization and activity of RNA-binding proteins orchestrates target gene expression at multiple levels to regulate different steps of myogenesis. Dysfunctions of these post-transcriptional regulators impair muscle development and homeostasis, but also cause defects in motor neurons or the neuromuscular junction, resulting in muscle degeneration and neuromuscular disease. Many RNA-binding proteins, such as members of the muscle blind-like (MBNL) and CUG-BP and ETR-3-like factors (CELF) families, display both overlapping and distinct targets in muscle cells. Thus they function either cooperatively or antagonistically to coordinate myoblast proliferation and differentiation. Evidence is accumulating that the dynamic interplay of their regulatory activity may control the progression of myogenic program as well as stem cell quiescence and activation. Moreover, the role of RNA-binding proteins that regulate post-transcriptional modification in the myogenic program is far less understood as compared with transcription factors involved in myogenic specification and differentiation. Here we review past achievements and recent advances in understanding the functions of RNA-binding proteins during skeletal muscle development, regeneration and disease, with the aim to identify the fundamental questions that are still open for further investigations.

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Staufen Impairs Autophagy in Neurodegeneration

Paul

Dansithong

Gandelman

et al. 2022

Annals of Neurology

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Objective The mechanistic target of rapamycin (mTOR) kinase is one of the master coordinators of cellular stress responses, regulating metabolism, autophagy, and apoptosis. We recently reported that staufen1 (STAU1), a stress granule (SG) protein, was overabundant in fibroblast cell lines from patients with spinocerebellar ataxia type 2 (SCA2), amyotrophic lateral sclerosis, frontotemporal degeneration, Huntington's, Alzheimer's, and Parkinson's diseases as well as animal models, and patient tissues. STAU1 overabundance is associated with mTOR hyperactivation and links SG formation with autophagy. Our objective was to determine the mechanism of mTOR regulation by STAU1. Methods We determined STAU1 abundance with disease‐ and chemical‐induced cellular stressors in patient cells and animal models. We also used RNA‐binding assays to contextualize STAU1 interaction with MTOR mRNA. Results STAU1 and mTOR were overabundant in bacterial artificial chromosome (BAC)‐C9ORF72, ATXN2Q127, and Thy1‐TDP‐43 transgenic mouse models. Reducing STAU1 levels in these mice normalized mTOR levels and activity and autophagy‐related marker proteins. We also saw increased STAU1 levels in HEK293 cells transfected to express C9ORF72‐relevant dipeptide repeats (DPRs). Conversely, DPR accumulations were not observed in cells treated by STAU1 RNA interference (RNAi). Overexpression of STAU1 in HEK293 cells increased mTOR levels through direct MTOR mRNA interaction, activating downstream targets and impairing autophagic flux. Targeting mTOR by rapamycin or RNAi normalized STAU1 abundance in an SCA2 cellular model. Interpretation STAU1 interaction with mTOR drives its hyperactivation and inhibits autophagic flux in multiple models of neurodegeneration. Staufen, therefore, constitutes a novel target to modulate mTOR activity and autophagy, and for the treatment of neurodegenerative diseases. ANN NEUROL 2023;93:398–416

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Differential regulation of autophagy by STAU1 in alveolar rhabdomyosarcoma and non‐transformed skeletal muscle cells

Cited by 10 publications

References 79 publications

The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events

The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events

RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

Staufen Impairs Autophagy in Neurodegeneration

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