Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma

Guo, Bing; Friedland, Scott; Alexander, W. B.; Myers, Jacquelyn A.; Wang, Wenjia; O’Dell, M.; Getman, Michael; Whitney-Miller, Christa L.; Agostini-Vulaj, Diana; Huber, Aaron R; Mello, Stephano S.; Vertino, Paula M.; Land, Hartmut; Steiner, Laurie A.; Hezel, Aram F.

doi:10.1016/j.celrep.2022.111253

Cited by 24 publications

(14 citation statements)

References 56 publications

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“…The top 12 genes were linked with two primary mechanisms: tumour suppressor pathway and regulation and oncogenic signalling and protein regulation: Tumour suppressor pathway and regulation: This group includes genes like PTEN, SMAD4, FBXW7 and SKP1, which are crucial for the control of cell growth, proliferation and survival. They exert a profound influence over cell cycle progression, DNA repair and the degradation of oncoproteins 43–46 Oncogenic signalling and protein regulation: This category includes genes such as MDM2, XPO1, HUWE1 and NEDD8, which are involved in oncogenic signalling and protein regulation pathways.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Liu,

Lu,

Qiu

et al. 2023

International Wound Journal

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Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co‐expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non‐fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.

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Section: Resultsmentioning

confidence: 99%

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Liu,

Lu,

Qiu

et al. 2023

International Wound Journal

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“…On the basis of BRAF inhibitors, combining MEK, RTK inhibitors, or chemotherapies could remarkably decrease the viability of tumoroid cells 241 . AT‐rich interaction domain 1A (ARID1A) is one of the subunits of the BRG1‐ or HBRM‐associated factor complex and has been demonstrated to have tumor suppressor effects 242,243 . ARID1A mutation or deficiency has been shown to contribute to facilitating the aggressiveness of tumors, 244 and it has been identified that most gastric cancer patients carry ARID1A mutations.…”

Section: Biomedical Applications Of Organoidsmentioning

confidence: 99%

“…241 AT-rich interaction domain 1A (ARID1A) is one of the subunits of the BRG1-or HBRM-associated factor complex and has been demonstrated to have tumor suppressor effects. 242,243 ARID1A mutation or deficiency has been shown to contribute to facilitating the aggressiveness of tumors, 244 and it has been identified that most gastric cancer patients carry ARID1A mutations. Recent research by Loe et al 245 provided a novel combination therapy of TP06 (epigenetic inhibitor) and Nutlin-3 (p53 agonist) to treat gastric tumoroids with Arid1a heterozygosity, exhibiting a robust inhibition of tumor growth.…”

Section: Drug Researchmentioning

confidence: 99%

Organoids: The current status and biomedical applications

Yang

Kung

et al. 2023

MedComm

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Organoids are three‐dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long‐term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large‐scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

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“…In addition to increased OXPHOS, enhanced anaerobic glycolysis (with increased Pgam1, pyruvate kinase M, and Pgk1 expression) has also been described in a lung cancer model with ARID1A loss, where a small-molecule bromodomain and extraterminal protein (BET) inhibitor (JQ1) was successful in treating tumor cells via glycolysis inhibition [393]. Furthermore, ARIDA1 affects several downstream pathways, such as [382,390,[394][395][396]:…”

Section: Arid1amentioning

confidence: 99%

“…ARID1A loss results in TGF-β inhibition, leading to increased cell proliferation [382,396]. TGF-β is a cytokine that, upon binding to one of its cell membrane receptors, TGF-β receptor type I or II, leads to intracellular SMAD signaling activation.…”

Section: Transforming Growth Factor β (Tgf-β)mentioning

confidence: 99%

The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies

Czegle

Huang

Soria

et al. 2023

Life

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There is an increasing understanding of the molecular and cytogenetic background of various tumors that helps us better conceptualize the pathogenesis of specific diseases. Additionally, in many cases, these molecular and cytogenetic alterations have diagnostic, prognostic, and/or therapeutic applications that are heavily used in clinical practice. Given that there is always room for improvement in cancer treatments and in cancer patient management, it is important to discover new therapeutic targets for affected individuals. In this review, we discuss mitochondrial changes in breast and gynecological (endometrial and ovarian) cancers. In addition, we review how the frequently altered genes in these diseases (BRCA1/2, HER2, PTEN, PIK3CA, CTNNB1, RAS, CTNNB1, FGFR, TP53, ARID1A, and TERT) affect the mitochondria, highlighting the possible associated individual therapeutic targets. With this approach, drugs targeting mitochondrial glucose or fatty acid metabolism, reactive oxygen species production, mitochondrial biogenesis, mtDNA transcription, mitophagy, or cell death pathways could provide further tailored treatment.

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Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma

Cited by 24 publications

References 56 publications

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Organoids: The current status and biomedical applications

The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies

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