β‑arrestin2 promotes 5‑FU‑induced apoptosis via the NF‑κB pathway in colorectal cancer

Ren, Weixia; Wang, Tingting; He, Xijing; Zhang, Qi; Zhou, Jianhua; Liu, Fangfang; Gao, Fangfang; Zhang, Yujun; Liu, Yulan

doi:10.3892/or.2018.6340

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…Arrb2 inhibits cell migration, invasion, and tumorigenesis via downregulation of the AKT signaling pathway in hepatocellular carcinoma [29], and its downregulation was associated with poorer prognosis in lung cancer patients [30]. Additionally, apoptosis through the NFκB pathway is promoted by Arrb2 in colorectal cancer [52]. The data in the present study strongly support that Arrb2 negatively regulates tumorigenic activities, including proliferation, migration, and angiogenesis, in GBM.…”

Section: Discussionsupporting

confidence: 78%

β-arrestin 2 stimulates degradation of HIF-1α and modulates tumor progression of glioblastoma

et al. 2021

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The basic function of β-arrestin 2 (Arrb2) is to negatively regulate the G-protein-coupled receptor signaling pathway through facilitating receptor desensitization and internalization. Arrb2 has also been reported to play various roles in cancer pathology including the proliferation, migration, invasion, metastasis, and apoptosis of solid tumors. However, the molecular mechanisms underlying the tumorigenic capacities of Arrb2 have not been elucidated. Here, we show a novel function of Arrb2: Arrb2 facilitates the degradation of HIF-1α, which is a master regulator of oxygen homeostasis. We also demonstrate that Arrb2 interacts with HIF-1α and stimulates ubiquitin-mediated 26S proteasomal degradation of HIF-1α by recruiting PHD2 and pVHL. Overexpression of Arrb2 in human glioblastoma cells suppresses HIF-1α signaling, tumor growth, and angiogenesis. Consistent with this antitumorigenic effect of Arrb2, low Arrb2 expression levels correlate with high HIF-1α expression and poor glioblastoma patient survival. These results collectively reveal a novel function of Arrb2 in the oxygensensing mechanism that directly regulates HIF-1α stability in human cancers and suggest Arrb2 as a new potential therapeutic target for glioblastoma.

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Section: Discussionsupporting

confidence: 78%

β-arrestin 2 stimulates degradation of HIF-1α and modulates tumor progression of glioblastoma

et al. 2021

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“…5-Fluorouracil (5-FU) represents the first-line treatment for CRC (Vodenkova et al, 2020). A recent study found that βarr2 levels were increased in CRC tissues compared with normal colon tissues (Ren et al, 2018). In vitro studies with CRC cell lines showed that knockdown of βarr2 expression resulted in a decrease in 5-FU-induced apoptosis, while overexpression of βarr2 promoted cancer cell apoptosis (Ren et al, 2018).…”

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confidence: 99%

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

Wess¹,

Oteng²,

Rivera‐Gonzalez³

et al. 2023

Pharmacol Rev

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The two β-arrestins, β-arrestin-1 and -2 (systematic names: arrestin-2 and -3, respectively), are multifunctional intracellular proteins that regulate the activity of a very large number of cellular signaling pathways and physiological functions. The two proteins were discovered for their ability to disrupt signaling via G protein-coupled receptors (GPCRs) via binding to the activated receptors. However, it is now well recognized that both β-arrestins can also act as direct modulators of numerous cellular processes via either GPCR-dependent orindependent mechanisms. Recent structural, biophysical, and biochemical studies have provided novel insights into how β-arrestins bind to activated GPCRs and downstream effector proteins.Studies with β-arrestin mutant mice have identified numerous physiological and pathophysiological processes regulated by β-arrestin-1 and/or -2. Following a short summary of recent structural studies, this review will primarily focus on β-arrestin-regulated physiological functions, with particular focus on the central nervous system and the roles of β-arrestins in carcinogenesis and key metabolic processes including the maintenance of glucose and energy homeostasis. This review will also highlight potential therapeutic implications of these studies and discuss strategies that could prove useful for targeting specific β-arrestin-regulated signaling pathways for therapeutic purposes.

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“…We identified the following hot spots for MetS in AAs. LDB1(LIM domain binding 1) known to regulate energy homoeostasis during diet-induced obesity [59], NPTN (neuroplastin) a gene that plays a role in signalling mechanisms [60], ARRB2 (arrestin beta 2), known to promote 5-FU-induced apoptosis via the NF-κB pathway in colorectal cancer [61], ITGB7 (integrin subunit beta 7) a gene that regulates multiple myeloma cell adhesion, migration, and invasion [62] (Figure 3). In Whites, we identified CREB1(cAMP responsive element binding protein 1 known to be associated with type 2 diabetes mellitus risk [63], NEDD4 (NEDD4 E3 ubiquitin protein ligase) which has an important role in controlling cell growth and in maintaining tissue homoeostasis [64], RAB4A (RAB4A, member RAS oncogene family), known to modulate the amiloride-sensitive sodium channel (ENaC) function in colonic epithelia [65] and STX1A (syntaxin 1A) known to play an essential role in biphasic exocytosis of the incretin hormone glucagon-like peptide 1 in type 2 diabetes [66] as an interactome hotspots (Figure 4) for MetS.…”

Section: Discussionmentioning

confidence: 99%

Race-specific alterations in DNA methylation among middle-aged African Americans and Whites with metabolic syndrome

et al. 2019

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Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors for all-cause mortality, cardiovascular disease, and cancer. Identifying epigenetic alterations associated with MetS in African Americans (AAs) and Whites may provide insight into genes that influence its differential health outcomes. We examined DNA methylation (DNAm) and performed an epigenome-wide association study (EWAS) of MetS among AAs and Whites with and without MetS. We assessed age, race and poverty status associated DNAm among AAs (n = 225) and White (n = 233) adults using NCEP-ATP III guidelines. Genome-wide DNAm measurement was assessed using Illumina Infinium Methylation EPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) were identified using dmpFinder and bumphunter. EWAS was performed using CpGassoc. We found significant DMPs associated with age, poverty status and MetS in each race. GSTT1(Glutathione S-Transferase Theta 1) was one of the top-hypermethylated genes and MIPEP (Mitochondrial Intermediate Peptidase) was one of the most hypomethylated genes when comparing AAs with and without MetS. PPP1R13L (Protein Phosphatase 1 Regulatory Subunit 13 Like) was the top hypermethylated and SCD (stearoyl-CoA desaturase-1) was one of the most hypomethylated genes for Whites with and without MetS. EWAS results showed that DNAm differences might contribute to MetS risk among Whites and AAs since different genes were identified in AAs and Whites. We replicated previously identified MetS associated genes and found that Thioredoxin-interacting protein (TXN1P) was statistically significantly differentially expressed only in Whites. Our results may be useful in further studies of genes underlying differences in MetS among AAs and Whites.

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β‑arrestin2 promotes 5‑FU‑induced apoptosis via the NF‑κB pathway in colorectal cancer

Cited by 8 publications

References 37 publications

β-arrestin 2 stimulates degradation of HIF-1α and modulates tumor progression of glioblastoma

β-arrestin 2 stimulates degradation of HIF-1α and modulates tumor progression of glioblastoma

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

Race-specific alterations in DNA methylation among middle-aged African Americans and Whites with metabolic syndrome

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