MicroRNA and ER stress in cancer

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 75, P. 3 - 14

Published: Jan. 9, 2021

Language: Английский

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Autophagy mediates ER stress and inflammation in Helicobacter pylori -related gastric cancer

Gut Microbes, Journal Year: 2021, Volume and Issue: 14(1)

Published: Dec. 29, 2021

Autophagy is a cellular degradation mechanism, which triggered by the bacterium Helicobacter pylori. A single nucleotide polymorphism (SNP) in autophagy gene ATG16L1 (rs2241880, G-allele) has been shown to dysregulate and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate role of this SNP H. pylori-mediated gastric carcinogenesis its molecular pathways. rs2241880 was genotyped subjects from different ethnic cohorts (Dutch Australian) presenting with (pre)malignant lesions various severity. Expression GRP78 (a marker for ER stress) assessed tissues. The effect on stress pro-inflammatory cytokine induction investigated organoids CRISPR/Cas9 modified cell lines. Development cancer associated G-allele. Intestinal metaplastic cells tissue patients showed increased levels ER-stress. In vitro models that pylori increases while reducing stress, appeared partly mediated genotype. pylori-induced IL-8 production TNF-α decreased, homozygous G-allele progression premalignant cancer. Modulation pathways mediators rs2441880 may underlie risk.

Language: Английский

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Unraveling the Molecular Nexus between GPCRs, ERS, and EMT

Mediators of Inflammation, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 23

Published: March 2, 2021

G protein-coupled receptors (GPCRs) represent a large family of transmembrane proteins that transduce an external stimulus into variety cellular responses. They play critical role in various pathological conditions humans, including cancer, by regulating number key processes involved tumor formation and progression. The epithelial-mesenchymal transition (EMT) is fundamental process promoting cancer cell invasion dissemination leading to metastasis, often intractable state the disease. Uncontrolled proliferation persistent metabolism cells also induce oxidative stress, hypoxia, depletion growth factors nutrients. These disturbances lead accumulation misfolded endoplasmic reticulum (ER) condition called ER stress (ERS) which counteracted activation unfolded protein response (UPR). Many GPCRs modulate ERS UPR signaling via sensors, IRE1α, PERK, ATF6, support survival inhibit death. By downstream pathways such as NF-κB, MAPK/ERK, PI3K/AKT, TGF-β, Wnt/β-catenin, upregulate mesenchymal transcription Snail, ZEB, Twist superfamilies regulate polarity, cytoskeleton remodeling, migration, invasion. Likewise, ERS-induced upregulates gene expression related EMT enhancing aggressiveness. Though are attractive therapeutic targets biology, much less known about their roles EMT. Here, we will discuss interplay GPCR-ERS linked cells, with particular focus on oncogenes molecular pathways.

Language: Английский

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Alcohol and Prostate Cancer: Time to Draw Conclusions

Biomolecules, Journal Year: 2022, Volume and Issue: 12(3), P. 375 - 375

Published: Feb. 28, 2022

It has been a long-standing debate in the research and medical societies whether alcohol consumption is linked to risk of prostate cancer (PCa). Many comprehensive studies from different geographical areas nationalities have shown that moderate heavy drinking positively correlated with development PCa. Nevertheless, some observations could not confirm such correlation exists; even suggest wine prevent or slow tumor growth. Here, we rigorously analyzed evidence both for against role PCa development. We found many epidemiological did consider other, potentially critical, factors, including diet (especially, low intake fish, vegetables linoleic acid, excessive use red meat), smoking, family history PCa, physical activity, high sexual activities especially early age first intercourse, sexually transmitted infections. In addition, discrepancies between come selectivity criteria control groups, questionnaires about type dosage alcohol, misreported consumption. The lifetime critical given typically slow-growing; however, show no association monitored only current relatively recent status. overall conclusion intake, binge drinking, associated increased this effect limited any beverage. Alcohol also directly lethality as it may accelerate growth tumors significantly shorten time progression metastatic Thus, recommend immediately quitting patients diagnosed discuss features metabolism tissue damaging ethanol metabolites on intracellular organization trafficking. review impact prostate-specific antigen level benign prostatic hyperplasia. Lastly, highlight known mechanisms interference carcinogenesis possible side effects during androgen deprivation therapy.

Language: Английский

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On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm

Cell Reports, Journal Year: 2022, Volume and Issue: 38(10), P. 110490 - 110490

Published: March 1, 2022

How metastatic cells arise is unclear. Here, we search for the induction of recently characterized pro-metastatic states as a surrogate origin metastasis. Since cell-death-inducing therapies can paradoxically promote metastasis, ask if such treatments induce in human colon cancer cells. We find that post-near-death acquire (PAMEs) and form distant metastases vivo. These PAME ("let's go" Greek) exhibit multifactorial cytokine storm well signs enhanced endoplasmic reticulum (ER) stress nuclear reprogramming, requiring CXCL8, INSL4, IL32, PERK-CHOP, NANOG. PAMEs neighboring tumor to become PAME-induced migratory (PIMs): highly re-enact enhance migration. Metastases are thus proposed originate from through intrinsic extrinsic cues tumoral ecosystem, driven by an impending cell-death experience involving ER modulation, paracrine recruitment via storm.

Language: Английский

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