Reactive oxygen species-mediated activation of the Src-epidermal growth factor receptor-Akt signaling cascade prevents bortezomib-induced apoptosis in hepatocellular carcinoma cells

Hou, Jinlin; Cui, Anguo; Song, Peiying; Hua, Hui; Luo, Ting; Jiang, Yangfu

doi:10.3892/mmr.2014.2736

Cited by 23 publications

(14 citation statements)

References 36 publications

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“…It has been proposed that ROS might modify tyrosine residues, further altering phosphorylation of many protein kinases involved in cell signaling (Akhand et al, ). In support of this notion, recent study reported that ROS mediates the activation of the Src‐EGFR pathway (Hou et al, ). In the present study, levels of ROS in BALF were increased after O 3 exposure.…”

Section: Discussionmentioning

confidence: 76%

“…In this case, O 3 exposure initially activated Src kinase, which in turn causes EGFR(Y845) phosphorylation leading to the subsequent autophosphorylation of EGFR(Y1068) (Wu et al, ). Another potential mechanism is suggested by O 3 ‐induced production of ROS (Hou et al, ). It has been proposed that ROS might modify tyrosine residues, further altering phosphorylation of many protein kinases involved in cell signaling (Akhand et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of ozone-induced lung inflammation by the epidermal growth factor receptor in mice

et al. 2015

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Human exposure to the highly reactive oxidant gas Ozone (O ) is associated with inflammatory responses in the airway epithelium. The mechanisms responsible have not been fully elucidated. Epidermal growth factor receptor (EGFR) has previously been shown to play a critical role in the pathogenesis of lung inflammation. To define the role of EGFR in O -induced lung inflammation in mice. 40 BALB/c mice were exposed to filtered air (FA) or (0.25, 0.5, 1.00 ppm) O for 3 h per day for 7 consecutive days. Levels of reactive oxygen species (ROS), EGF, and transforming growth factor α (TGF-α) in the bronchoalveolar lavage fluid (BALF) of mice were measured using ELISA. BALB/c mice were intratracheally instilled with the EGFR kinase inhibitor PD153035 2 h prior to O exposure and every other day thereafter. Phosphorylation of EGFR (Y1068) in lung sections was determined using immunohistochemical staining and western blot 24 h after exposure. Inhalation of O induced pronounced lung inflammation in a dose-dependent manner. Levels of ROS, TGF-α, and total proteins and cells in the BALF of mice exposed to 0.5 ppm or 1.0 ppm of O were markedly elevated relative to those in the BALF of the mice exposed to FA. In addition, exposure to O induced EGFR(Y1068) phosphorylation in the airway epithelium. Administration of PD153035 resulted in a significantly reduced lung inflammation as well as EGFR phosphorylation induced by O exposure. Inhalation of O leads to inflammatory responses that are dependent on the activation the EGFR in the airway epithelium. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2016-2027, 2016.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Regulation of ozone-induced lung inflammation by the epidermal growth factor receptor in mice

et al. 2015

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“…5a). IR exposure induces ROS generation and ROS activates Src/AKT [37,38]. To determine if IR-induced ROS was involved in Src/AKT phosphorylation and senescence induction in the absence of integrin β4, we treated cells with NAC, a ROS scavenger, prior to irradiation of RKO cells ( Supplementary Figure S7).…”

Section: Resultsmentioning

confidence: 99%

Integrin α6β4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues

et al. 2018

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Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. Many recent studies have demonstrated that cellular senescence plays a crucial role in the regression of tumors exposed to ionizing radiation (IR), but the underlying mechanism remains unknown. Here we show that the activation of integrin β4 is essential for IR-induced cellular senescence. IR treatment results in the phosphorylation of integrin β4 at tyrosine residue 1510, leading to activation of the integrin α6β4-Src-AKT signaling pathway. We further reveal that the IR-induced phosphorylation of integrin β4 is regulated by the cholesterol content and membrane fluidity. We also find that IR-induced p53-caspase signaling is independent of integrin α6β4-Src-AKT signaling. Finally, we show that siRNA- or inhibitor-mediated blockade of integrin α6β4-Src-AKT signaling switches the post-irradiation fate from senescence to apoptosis, under p53 activated condition, in both cancer cells and tumor tissues of xenograft mice. On the basis of our finding that, integrin α6β4 is specifically activated and acts primarily to induce premature senescence in irradiated cancer cells, we propose that this integrin may be a valuable target and biomarker for radiotherapy.

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“…It has been reported that ROS/RNS can attack key biological molecules (including EGFR, NLR inflammasome) and modulate many signaling pathways (such as NF‐κB signaling) (Dostert et al, ; Wu et al, ; Hou et al, ). EGFR, a pivotal growth factor receptor possessing intrinsic tyrosine kinase activity, is a transmembrane protein and can be directly activated or transactivated in response to various of stimuli (Gschwind et al, ).…”

Section: Discussionmentioning

confidence: 99%

Involvement of EGF receptor signaling and NLRP12 inflammasome in fine particulate matter‐induced lung inflammation in mice

Jin

Zhang

et al. 2016

Environmental Toxicology

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Epidemiological studies have shown that exposure to ambient fine particulate matter (PM ) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM exposure. However, the mechanisms underlying PM -induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM -induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM suspension (4.0 mg/kg b.w.) for 5 consecutive days, respectively. Bronchoalveolar lavage (BAL) was conducted and BAL fluid (BALF) was collected. The levels of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), epidermal growth factor (EGF), CXCL1, interleukin (IL)-1β, and IL-18 in BALF were determined using ELISA. mRNA levels of IL-6, IL-1β, IL-18, CXCL1, IL-10, NLRP3, Caspase-1, and NLRP12 in lung tissues were determined by RT-PCR. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) in lung tissues were examined using immunohistochemical staining and Western blotting, respectively. Protein levels of Caspase-1, NLRP3, NF-κB-p52/p100, and NF-κB-p65 in bronchial epithelium were examined using immunohistochemical staining. It was shown that PM exposure induced lung inflammation. Levels of total protein, ROS, iNOS, EGF, and CXCL1 and cell number in the BALF of mice exposed to PM were markedly elevated relative to the control. mRNA levels of CXCL1, IL-1β, and IL-18 in lung tissues of PM -exposed mice were increased in comparison with the control. However, level of NLRP12 mRNA in lung tissues of PM -exposed mice was reduced. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) levels in the lungs of PM -instilled mice were higher than those in the lungs of the control. The protein levels of NF-κB-p52/p100 and NF-κB-p65 in bronchial epithelium of PM -exposed mice were also increased compared with the control. This study suggests that EGF-EGFR-Akt-NF-κB signaling and NLRP12 inflammasome may be associated with PM -induced lung inflammation in mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121-1134, 2017.

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Reactive oxygen species-mediated activation of the Src-epidermal growth factor receptor-Akt signaling cascade prevents bortezomib-induced apoptosis in hepatocellular carcinoma cells

Cited by 23 publications

References 36 publications

Regulation of ozone-induced lung inflammation by the epidermal growth factor receptor in mice

Regulation of ozone-induced lung inflammation by the epidermal growth factor receptor in mice

Integrin α6β4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues

Involvement of EGF receptor signaling and NLRP12 inflammasome in fine particulate matter‐induced lung inflammation in mice

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