Arsenite and Cadmium Activate MAPK/ERK via Membrane Estrogen Receptors and G-Protein Coupled Estrogen Receptor Signaling in Human Lung Adenocarcinoma Cells

Huff, Mary O.; Todd, Sarah; Smith, Aaron L.; Elpers, Julie T.; Smith, Alexander P.; Murphy, Ray; Bleser-Shartzer, Allison S.; Hoerter, Jacob E.; Radde, Brandie N.; Klinge, Carolyn M.

doi:10.1093/toxsci/kfw064

Cited by 58 publications

(39 citation statements)

References 68 publications

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“…For instance, Huang et al found one of chemokines, TGF-β1, could ameliorate Cd-induced nephrotoxicity [40]. Meanwhile, Huff et al showed that arsenate and Cd could activate G-protein coupled estrogen receptor signaling in human lung adenocarcinoma cells [41]. Our results are consistent with these findings.…”

Section: Discussionsupporting

confidence: 89%

The Dysbiosis of Gut Microbiota Caused by Low-Dose Cadmium Aggravate the Injury of Mice Liver through Increasing Intestinal Permeability

Liu

Xia

et al. 2020

Microorganisms

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Cadmium (Cd), widely present in food and drinking water at low doses, can cause health risks. However, the mechanistic effects of long-term Cd exposure at low dose through dietary intake is poorly studied. The aim of this study is to elucidate whether the dysbiosis of gut microbiota caused by Cd at an environmental low dose can aggravate the injury of mice liver, and the possible mechanism is investigated. In order to explore the potential underlying mechanism, the analyses of the variation of gut microbiota composition, intestinal permeability, and hepatic transcriptome were conducted. Our results showed that gut microbiota was disturbed. The rise of intestinal permeability induced by the dysbiosis of gut microbiota resulted in more Cd ions accumulating in mice liver, but it could be restored partly through depleting gut microbiota by antibiotics cocktail. Transcriptomic analyses indicated that 162 genes were significantly differentially expressed including 59 up-regulated and 103 down-regulated in Cd treatment. These genes were involved in several important pathways. Our findings provide a better understanding about the health risks of cadmium in the environment.

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Section: Discussionsupporting

confidence: 89%

The Dysbiosis of Gut Microbiota Caused by Low-Dose Cadmium Aggravate the Injury of Mice Liver through Increasing Intestinal Permeability

Liu

Xia

et al. 2020

Microorganisms

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“…Moreover, a clinical investigation revealed that postmenopausal women who received estrogen plus progestin treatment exhibit an increased number of deaths from lung cancer [ 42 ]. The estrogen signaling pathway was also involved in cellular cytoskeleton organization [ 43 ] and cross-talk with the MAPK signaling pathway [ 44 ]. Taken together, biological function analyses of these six miRNAs strongly suggest critical roles in LUAD, which may provide a new strategy for LUAD diagnosis and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNAs as potential biomarkers for lung adenocarcinoma using integrating genomics analysis

et al. 2017

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Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer, but novel biomarkers for early diagnosis are lacking. Extensive effort has been exerted to identify miRNA biomarkers in LUAD. Unfortunately, high inter-lab variability and small sample sizes have produced inconsistent conclusions in this field. To resolve the above-mentioned limitations, we performed a comprehensive analysis based on LUAD miRNome profiling studies using the robust rank aggregation (RRA) method. Moreover, miRNA-gene interaction network, pathway enrichment analysis and Kaplan-Meier survival curves were used to investigate the clinical values and biological functions of the identified miRNAs. A total of six common differentially expressed miRNAs (DEMs) were identified in LUAD. An independent cohort further confirmed that four miRNAs (miR-21-5p, miR-210-3p, miR-182-5p and miR-183-5p) were up-regulated and two miRNAs (miR-126-3p and miR-218-5p) were down-regulated in LUAD tissues. Pathway enrichment analysis also suggested that the above-listed six DEMs may affect LUAD progression via the estrogen signaling pathway. Survival analysis based on the TCGA dataset revealed the potential prognostic values of six DEMs in patients with LUAD (P-value<0.01). In conclusion, we identified a panel of six miRNAs from LUAD using miRNome profiling studies. Our results provide evidence for the use of these six DEMs as novel diagnostic and prognostic biomarkers for LUAD patients.

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“…Many studies have shown that ERβ is significantly higher in NSCLC tissues and was associated with poor prognosis in NSCLC patients . Overexpression of ERβ is associated with the expression of p‐44/42 MAPK in lung cancer, which can promote cell proliferation and invasion and inhibit cell apoptosis in lung cancer cells . It has been reported that ERβ and IL‐6 can promote the progression of NSCLC by activating the two signaling pathways of JAK2/STAT3 and MEK/ERK, but which ERβ subtype plays a role in NSCLC remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Interaction of estrogen receptor β5 and interleukin 6 receptor in the progression of non–small cell lung cancer

Tang

Bai

Xiong

et al. 2018

J of Cellular Biochemistry

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Numerous studies have shown that the estrogen receptor beta (ERβ) and interleukin 6 receptor (IL-6R) had interaction in many tumors, including lung cancer. Previous studies found that ERβ5 exhibits a different biological function compared with the other subtypes of ERβ. Therefore, this study mainly explores the interaction between ERβ5 and IL-6R in the progression of lung cancer. We found that the expression of ERβ5, IL-6 and glycoprotein 130 (GP130) were significantly increased (P < 0.001) and the 5-year survival rate with the co-expression of ERβ5 and GP130 is significantly lower (P = 0.0315) in non-small cell lung cancer (NSCLC) patients. The cell proliferation, invasion, and cell cycle were markedly increased, and the cell apoptotic was markedly inhibited with the concurrent action of ERβ5 and IL-6 in A549 cells (P < 0.05). In addition, the expression of ERβ5, GP130, p-AKT, and p-44/42 MAPK was also significantly increased in A549 cells (P < 0.05). These results indicate that ERβ5 and GP130 can synergistically promote the progression of NSCLC and maybe combined as an independent prognostic factor in patients. In addition, these results also provide a theoretical basis for the combined targeting therapy of ERβ5 and GP130 in NSCLC.

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Arsenite and Cadmium Activate MAPK/ERK via Membrane Estrogen Receptors and G-Protein Coupled Estrogen Receptor Signaling in Human Lung Adenocarcinoma Cells

Cited by 58 publications

References 68 publications

The Dysbiosis of Gut Microbiota Caused by Low-Dose Cadmium Aggravate the Injury of Mice Liver through Increasing Intestinal Permeability

The Dysbiosis of Gut Microbiota Caused by Low-Dose Cadmium Aggravate the Injury of Mice Liver through Increasing Intestinal Permeability

Identification of microRNAs as potential biomarkers for lung adenocarcinoma using integrating genomics analysis

Interaction of estrogen receptor β5 and interleukin 6 receptor in the progression of non–small cell lung cancer

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