NF-κB pathway link with ER stress-induced autophagy and apoptosis in cervical tumor cells

Zhu, Xiaolan; Huang, Li; Gong, Jie; Shi, Chun; Wang, Zhiming; Ye, Bingkun; Xuan, Aiguo; He, Xiaosong; Long, Dahong; Zhu, Xiao; Ma, Ning‐Fang; Leng, Shuilong

doi:10.1038/cddiscovery.2017.59

Cited by 54 publications

(36 citation statements)

References 39 publications

(37 reference statements)

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“…The link between NF-κB and autophagy in the current work might have been established in Cd group. Concordantly, Quinazolinediamine which is an NF-κB inhibitor had been proved to ameliorate both autophagy and apoptosis induced by brefeldin [31]. Agreeing with the results of this work the relation between Sildenafil and NF-κB, it had been proved that Roflumilast, a phosphodiesterase4 inhibitor, might mitigate cadmium-induced renal toxicity via modulation of NF-κB activation and induction of NQO1 in rats [3,28].…”

Section: Discussionsupporting

confidence: 56%

Cadmium-induced adrenal cortical autophagy in rats: possible modulation by sildenafil

Imam

Motawei

2020

Folia Morphol

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Background: The link between autophagy, inflammatory bowel disease, ischemic injury and cancer had been established. Reasonable evidence is available for Cadmium (Cd) to be related to certain cancers. Sildenafil had been investigated to modulate oxidative stress mechanisms. Aim of work: is to investigate Cadmiuminduced adrenal cortical autophagy and to declare possible modulation by sildenafil. Material and methods: Twenty four Wistar rats weighing 150-200gm were randomly and equally assigned into: Control group, Sildenafil (20mg/kg/day orally) exposed group, Cadmium group (Cd chloride 1mg/kg/day Sc), Cadmium + Sildenafil group (rats received Cd concomitant with Sildenafil). Euthanasia was done 4 weeks from the beginning of experiment; adrenal glands were subjected to biochemical, histological, ultrastructural and immunnohistochemical assessment. Results: Control and Sildenafil exposed groups exhibited nearly similar results. Cd had produced adrenal cortical apoptosis and ultrastructural derangement of cell organelles. Cd-induced autophagy was detected by ultrastructural abundance of enlarged lysosomes and significant (p<0.05) increase in the optical density of LAMP2 (Lysosomal associated membrane protein2) immunoexpression. Sildenafil taken with Cd had decreased adrenal cortical autophagy, significantly modulated the adrenal gland Superoxide dismutase (SOD) and Malondialdehyde (MDA) compared to Cd group. Also, the optical density of NF-κb and Caspase3 immunoexpression was significantly decreased in Cd+Sildenafil compared to Cd group. 1 Conclusions: Cadmium might induce adrenal cortical autophagy in rats and Sildenafil might show an ameliorating effect probably through enhancement of antioxidant defense mechanism and modulation of NF-κb.

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Section: Discussionsupporting

confidence: 56%

Cadmium-induced adrenal cortical autophagy in rats: possible modulation by sildenafil

Imam

Motawei

2020

Folia Morphol

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“…The results indicate the involvement of NF‐κB in HIF‐1 α activation for late generation Cell Line A. It has been reported that NF‐κB activation could be induced by ER stress or unfolded protein response . In this study, RNAseq analysis detected age‐correlated overexpression of the ER stress marker ATF4 in Cell Line A but not in Cell Line B ( p = 4.64 × 10 −17 ).…”

Section: Discussionmentioning

confidence: 53%

HIF‐1 Signaling Pathway Implicated in Phenotypic Instability in a Chinese Hamster Ovary Production Cell Line

Lieske

Wei

Crowe

et al. 2020

Biotechnology Journal

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Monitoring genotypic and phenotypic stability is crucial during the development of recombinant Chinese hamster ovary (CHO) cell lines. Although genotypic instability is well‐studied, there are few reports on phenotypic instability. Here, a case study of two clonal cell lines derived from Pfizer's site‐specific integration expression platform that expresses the same monoclonal antibody is described. It is shown that both cell lines (herein referred to as “Cell Line A” and “Cell Line B”) are genotypically stable up to 130 generations. However, when both cell lines are run side‐by‐side in a fed‐batch production assay, productivity from Cell Line A later generation cells is much lower when compared to earlier generation cells. Phenotypically, later generation Cell Line A cells display increased lactate production, decreased productivity, and decreased cell viability. Metabolic analysis reveals that Cell Line A exhibits increased glycolysis activity and capacity at higher generational age. Whole transcriptomic sequencing shows significant upregulation of the hypoxia‐inducible factor 1‐alpha (HIF‐1α) signaling pathway and associated downstream targets. Furthermore, Western blot analysis confirms elevated HIF‐1α protein in Cell Line A cells at later generation. These results suggest a novel role for HIF‐1α in the age‐associated metabolic changes that result in the phenotypic instability of a recombinant CHO cell line.

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“…Interestingly, the cell surface localization of MT1‐MMP, rather than its proteolytic processing, was found to contribute to the ER stress induction process . In support, ER stress‐induced autophagy and apoptosis in cervical tumor cells was recently reported . Intriguingly, the biological significance of the transient ARP101‐mediated formation of MT1‐MMP dimers followed by the formation of MT1‐MMP tetramers at higher ARP101 concentrations remains unknown.…”

Section: Discussionmentioning

confidence: 92%

Dual functions of ARP101 in targeting membrane type‐1 matrix metalloproteinase: Impact on U87 glioblastoma cell invasion and autophagy signaling

Desjarlais

Annabi

2018

Chem Biol Drug Des

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Abbreviations: ATG, autophagy-related proteins; ConA, concanavalin-A; ECM, extracellular matrix; MT1-MMP, membrane type-1 matrix metalloproteinase. Abstract Membrane type-1 matrix metalloproteinase (MT1-MMP) possesses both extracellular proteolytic and intracellular signal-transducing functions in tumorigenesis. An imbalance in MT1-MMP expression and/or function triggers a metastatic, invasive, and therapy resistance phenotype. MT1-MMP is involved in extracellular matrix (ECM) proteolysis, activation of latent MMPs, as well as in autophagy signaling in human hepatoma and glioblastoma cells. A low autophagy index in tumorigenesis has been inferred by recent studies where autophagic capacity was decreased during tumor progression. Here, we establish ARP101 as a dual-function small-molecule inhibitor against MT1-MMP ECM hydrolysis and autophagy signal-transducing functions in a model of grade IV glioblastoma cells. ARP101 inhibited concanavalin-A-mediated proMMP-2 activation into MMP-2, as well as MT1-MMP auto-proteolytic processing. When overexpressing recombinant Wt MT1-MMP, ARP101 inhibited proMMP-2 activation and triggered the formation of MT1-MMP oligomers that required trafficking to the plasma membrane. ARP101 further induced cell autophagy as reflected by increased formation of acidic vacuole organelles, LC3 puncta, and autophagy-related protein ATG9 transcription. These were all significantly reversed upon siRNA-mediated gene silencing of MT1-MMP. ARP101 can thus concomitantly inhibit MT1-MMP extracellular catalytic function and exploit its intracellular transducing signal function to trigger autophagy-mediated cell death in U87 glioblastoma cancer cells. K E Y W O R D S ARP101, autophagy, concanavalin-A, glioblastoma, MT1-MMP processing How to cite this article: Desjarlais M, Annabi B. Dual functions of ARP101 in targeting membrane type-1 matrix metalloproteinase: Impact on U87 glioblastoma cell invasion and autophagy signaling. Chem Biol Drug Des. 2019;93:272-282. https://doi.

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NF-κB pathway link with ER stress-induced autophagy and apoptosis in cervical tumor cells

Cited by 54 publications

References 39 publications

Cadmium-induced adrenal cortical autophagy in rats: possible modulation by sildenafil

Cadmium-induced adrenal cortical autophagy in rats: possible modulation by sildenafil

HIF‐1 Signaling Pathway Implicated in Phenotypic Instability in a Chinese Hamster Ovary Production Cell Line

Dual functions of ARP101 in targeting membrane type‐1 matrix metalloproteinase: Impact on U87 glioblastoma cell invasion and autophagy signaling

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