Cancer and ER stress: Mutual crosstalk between autophagy, oxidative stress and inflammatory response

Lin, Yu‐Hsuan; Jiang, Mei; Chen, Wanjun; Zhao, Tiejian; Wei, Yanfei

doi:10.1016/j.biopha.2019.109249

Cited by 319 publications

(242 citation statements)

References 124 publications

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“…Patients with esophageal reflux may be more likely to suffer an increase in FGF19, and all the factors that induced ER stress may facilitate the upregulation of FGF19 and eventually leads to a vicious circle, since increased FGF19, in turn, will promote tumor progression. This is in accordance with results reported that ER acts as a moving organelle with many important cellular functions [33] and FGF19 was reported to protect hepatocellular carcinoma cells against ER stress [12]. Our study established an FGF19-overproducing model to mimic the more malignant phenotype of FGF19-overexpressed LSQ.…”

Section: Discussionsupporting

confidence: 92%

Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104

Fan

Han

et al. 2020

Oncogene

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Lung cancer occurrence and associated mortality ranks top in all countries. Despite the rapid development of targeted and immune therapies, many patients experience relapse within a few years. It is urgent to uncover the mechanisms that drive lung cancer progression and identify novel molecular targets. Our group has previously identified FGF19 as a prognostic marker and potential driver gene of lung squamous cell carcinomas (LSQ) in Chinese smoking patients. However, the underlying mechanism of how FGF19 promotes the progression of LSQ remains unclear. In this study, we characterized and confirmed that FGF19 serves as an oncogenic driver in LSQ development and progression, and reported that the amplification and high expression of FGF19 in LSQ was significantly associated with poor overall and progression-free survival. A higher serum level of FGF19 was found in lung cancer patients, which could also serve as a novel diagnostic index to screen lung cancer. Overproduction of FGF19 in LSQ cells markedly promoted cell growth, progression and metastasis, while downregulating FGF19 effectively inhibited LSQ progression in vitro and in vivo. Moreover, downregulating the receptor FGFR4 was also effective to suppress the growth and migration of LSQ cells. Since FGF19 could be induced by smoking or endoplasmic reticulum stress, to tackle the more malignant FGF19-overproducing LSQ, we reported for the first time that inhibiting mTOR pathway by using AZD2014 was effective and feasible. These findings have offered a new strategy by using anti-FGF19/FGFR4 therapy or mTOR-based therapy in FGF19-driven LSQ.

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Section: Discussionsupporting

confidence: 92%

Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104

Fan

Han

et al. 2020

Oncogene

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“…Additionally, IL-6 can increase nitric oxide synthase (iNOS)-mediated nitric oxide production, resulting in DNA damage [77] and cyclic oxygenase (COX)-2-mediated prostaglandin secretion that results in cell growth, antiapoptosis and angiogenesis [78]. Autophagy plays a relevant role in inflammation, although understanding of this interconnection is still incomplete [79]. Many of the signaling pathways that control inflammation during tumorigenesis are also known regulators of autophagy.…”

Section: Cholangiocarcinoma Genetic and Epigenetic Alterations And Aumentioning

confidence: 99%

“…This correlation between IL-6-mediated carcinogenesis and autophagy may represent an interesting and promising approach to treat iCCA with an inflammatory component. Additionally, there are a large number of studies that relate different pro-inflammatory pathways with ER stress and autophagy [79,81,82].…”

Section: Cholangiocarcinoma Genetic and Epigenetic Alterations And Aumentioning

confidence: 99%

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Pérez‐Montoyo

2020

Cells

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Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumor microenvironment, but also to increase invasiveness and resistance to anticancer drugs such as chemotherapy. This review collects clinical evidence of autophagy deregulation during cholangiocarcinogenesis together with preclinical reports evaluating compounds that modulate autophagy to induce cholangiocarcinoma (CCA) cell death. Altogether, experimental data suggest an impairment of autophagy during initial steps of CCA development and increased expression of autophagy markers on established tumors and in invasive phenotypes. Preclinical efficacy of autophagy modulators promoting CCA cell death, reducing invasiveness capacity and resensitizing CCA cells to chemotherapy open novel therapeutic avenues to design more specific and efficient strategies to treat this aggressive cancer.

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“…Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis and apoptosis decision of malignancy [6,7]. The ER is a crucial organelle for multiple cellular processes.…”

Section: Introductionmentioning

confidence: 99%

“…ER stress is induced by alterations in ER homeostasis, and overwhelming exogenous or endogenous stress can lead to inappropriate function. The physiological role of ER stress is to restore the organelle's homeostasis; however, sustained or chronic ER stress can trigger cell death program involving apoptosis [6,7]. Malignant glioma maintains ER homeostasis with an aim to suppress ER stress-induced apoptotic cell death [8].…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Contributes to Indomethacin-Induced Glioma Apoptosis

Chang

et al. 2020

IJMS

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The dormancy of cellular apoptotic machinery has been highlighted as a crucial factor in therapeutic resistance, recurrence, and poor prognosis in patients with malignancy, such as malignant glioma. Increasing evidence indicates that nonsteroidal anti-inflammatory drugs (NSAIDs) confer chemopreventive effects, and indomethacin has been shown to have a novel chemotherapeutic application targeting glioma cells. To extend these findings, herein, we studied the underlying mechanisms of apoptosis activation caused by indomethacin in human H4 and U87 glioma cells. We found that the glioma cell-killing effects of indomethacin involved both death receptor- and mitochondria-mediated apoptotic cascades. Indomethacin-induced glioma cell apoptosis was accompanied by a series of biochemical changes, including reactive oxygen species generation, endoplasmic reticulum (ER) stress, apoptosis signal-regulating kinase-1 (Ask1) activation, p38 hyperphosphorylation, protein phosphatase 2A (PP2A) activation, Akt dephosphorylation, Mcl-1 and FLICE-inhibiting protein (FLIP) downregulation, Bax mitochondrial distribution, and caspases 3/caspase 8/caspase 9 activation. Data on pharmacological inhibition related to oxidative stress, ER stress, free Ca2+, and p38 revealed that the axis of oxidative stress/ER stress/Ask1/p38/PP2A/Akt comprised an apoptotic cascade leading to Mcl-1/FLIP downregulation and glioma apoptosis. Since indomethacin is an emerging choice in chemotherapy and its antineoplastic effects have been demonstrated in glioma tumor-bearing models, the findings further strengthen the argument for turning on the aforementioned axis in order to activate the apoptotic machinery of glioma cells.

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Cancer and ER stress: Mutual crosstalk between autophagy, oxidative stress and inflammatory response

Cited by 319 publications

References 124 publications

Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104

Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Endoplasmic Reticulum Stress Contributes to Indomethacin-Induced Glioma Apoptosis

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