The Influence of Heavy Metals on Gastric Tumorigenesis

Wang, Liang; Miao, Congxiu; He, Yonghong; Li, Hanglong; Zhang, Shasha; Li, Keyan; Liu, Huimin; Li, Wushuang; Zhao, Jiangman; Xu, Yue; Tang, Hui; Zhou, Qiang

doi:10.1155/2022/6425133

Cited by 8 publications

(13 citation statements)

References 57 publications

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“…Expression. To confirm the mechanism through which chronic Tl acetate exposure induces malignant transformation, we first observed increased levels of m 6 A modification with an increase in cell passage number (Figure 6A,B). Chronic Tl acetate exposure induced a significant increase in the mRNA and protein levels of ATP13A3 with an increase in cell passage number (Supplementary Figure 14A,B).…”

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 87%

“…In addition, treating the transformed cells with a global methylation inhibitor [3-deazaadenosine (DAA)] substantially reduced the m 6 6K and Supplementary Figure 14D). Thus, our data demonstrated that an increase in the m 6 A writer complex (METTL3 and METTL14) and a decrease in the eraser ALKBH5 induced by chronic Tl acetate exposure in transformed cells promote increases in the m 6 A modification and expression levels of ATP13A3.…”

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

“…As expected, the m 6 A levels and mRNA half-life of ATP13A3 were dramatically promoted with an increase in the passage number of the transformed cells (Figure 6C,D). Because m 6 A writers, erasers, and readers play crucial roles in gene expression by catalyzing m 6 A formation in RNAs, we first evaluated the correlation between 14 key m 6 A-related genes and the ATP13A3 levels. The ATP13A3 level was significantly correlated with many m 6 A-related genes in the GTEx, TCGA, and in-house RNA-Seq data sets, including METTL3, METTL14, and ALKBH5 (Figure 6E).…”

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

“…Furthermore, we found a correlation between chronic Tl-induced overexpression of ATP13A3, METTL3, and METTL14 and the low level of expression of ALKBH5 based on the transformed cells and xenograft tumors (Supplementary Figure 14C and Figure 6F). In addition, the m 6 A levels and the mRNA and the protein levels of ATP13A3 and m 6 A-related genes (METTL3 and ALKBH5) were unchanged in cells treated with Sn or Zn, emphasizing the special mechanisms through which Tl exerts colorectal toxicological effects (Supplementary Figure 15). In addition, treating the transformed cells with a global methylation inhibitor [3-deazaadenosine (DAA)] substantially reduced the m 6 6K and Supplementary Figure 14D).…”

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

“…In addition, the m 6 A levels and the mRNA and the protein levels of ATP13A3 and m 6 A-related genes (METTL3 and ALKBH5) were unchanged in cells treated with Sn or Zn, emphasizing the special mechanisms through which Tl exerts colorectal toxicological effects (Supplementary Figure 15). In addition, treating the transformed cells with a global methylation inhibitor [3-deazaadenosine (DAA)] substantially reduced the m 6 6K and Supplementary Figure 14D). Thus, our data demonstrated that an increase in the m 6 A writer complex (METTL3 and METTL14) and a decrease in the eraser ALKBH5 induced by chronic Tl acetate exposure in transformed cells promote increases in the m 6 A modification and expression levels of ATP13A3.…”

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

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Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Chen

et al. 2023

Environ. Sci. Technol.

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Element contamination, including that from heavy metals, is associated with gastrointestinal tumorigenesis, but the effects and mechanisms of crucial element exposure associated with colorectal cancer remain unclear. We profiled 56 elements by ICP-MS and used logistic regression, LASSO, BKMR, and GAM to identify colorectal cancer-relevant elements. A series of biochemical experiments were performed to demonstrate the cytotoxicity and the mechanisms of malignant transformation after metal exposure. Using an elementomics approach, we first found that the metal thallium (Tl) was positively correlated with many toxic metals and was associated with a significantly increased risk of colorectal cancer. Acute exposure to Tl induced cytotoxicity and cell death by accelerating the generation of reactive oxygen species and DNA damage. Chronic exposure to Tl led to the inhibition of cell death and thereby induced the malignant transformation of normal colon cells and xenograft tumor formation in nude mice. Furthermore, we describe the first identification of a significant metal quantitative trait locus for the novel colorectal cancer susceptibility locus rs1511625 near ATP13A3. Mechanistically, Tl increased the level of aberrant N 6 -methyladenosine (m 6 A) modification of ATP13A3 via the METLL3/ METTL14/ALKBH5-ATP13A3 axis to promote colorectal tumorigenesis. This study provides a basis for the development of public health strategies for reducing metal exposure among populations at high risk for colorectal cancer.

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Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 87%

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

Section: Chronic Tl Acetate Exposure Increases the Level Of N 6 -Meth...mentioning

confidence: 99%

See 3 more Smart Citations

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Chen

et al. 2023

Environ. Sci. Technol.

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Quantitative distribution of essential elements and non-essential metals in breast cancer tissues by LA-ICP-TOF–MS

Escudero-Cernuda,

Clases,

Eiro

et al. 2024

Anal Bioanal Chem

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Breast cancer (BC) is the leading cause of cancer death among women worldwide, making the discovery and quantification of new biomarkers essential for improving diagnostic and preventive strategies to limit dissemination and improve prognosis. Essential trace metals such as Fe, Cu, and Zn may play critical roles in the pathophysiology of both benign and malignant breast tumors. However, due to the high metabolic activity and reduced element selectivity of cancer cells, also non-essential elements may be taken up and may even be implicated with disease progression. This study investigates the spatial distribution and concentrations of both essential and non-essential elements in breast tissues, assessing their potential for diagnostic applications. Laser ablation (LA)–inductively coupled plasma–mass spectrometry (ICP-MS) with a time-of-flight (ToF) mass analyzer (LA-ICP-ToF–MS) was used to inquire the distribution of almost all elements across the periodic table and their abundance in metastatic (n = 11), non-metastatic (n = 7), and healthy (n = 4) breast tissues. Quantification was achieved using gelatine-based standards for external calibration to quantitatively map various elements. Overall, the Fe, Cu, Zn, Sr, and Ba levels were significantly increased in tumor samples with Sr and Ba showing strong correlation, likely due to their similar chemistry. Comparison of calibrated LA-ICP-ToF–MS data with a histologic staining demonstrated the possibility to clearly differentiate between various tissue types and structures in breast tissues such as tumor niche and stroma. The levels of the studied elements were significantly higher in the tumor niche areas compared to the stroma, and for Fe, a significant accumulation was observed in the tumor niche areas from the metastatic patient group relative to the levels found in the same areas of the non-metastatic group. Graphical Abstract LA-ICP-ToF–MS was used to quantitatively map the biodistribution of essential and non-essential elements in metastatic and non-metastatic breast cancer tissues.

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Heavy metals in biological samples of cancer patients: a systematic literature review

Coradduzza,

Congiargiu,

Azara

et al. 2024

Biometals

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The majority of the so-called heavy metals are suspected to be involved in a number of pathologies and play a role in human carcinogenesis. Some of them (i.e. arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg) and nickel (Ni)) have been defined as carcinogens, increasing the susceptibility of tumor development and progression in humans. Moreover, Ni, Cr, Cd, Hg, and Pb together with zinc (Zn) and iron (Fe), may be capable of stimulating the progression of breast cancer and reducing a patient’s sensitivity to treatment through alterations to DNA methylation. In patients with gastric cancers, levels of various heavy metals are augmented and hypothesized to amplify the expression of the human epidermal growth factor receptor type 2 gene. Cd may increase the risk of lung cancer development and have a negative impact on the overall survival of lung cancer patients. To investigate the relation between heavy metals in biological samples and risk, occurrence and survival cancer individuals, a comprehensive review work was performed, with a focus on breast, lung, prostate and gastric cancers. An extensive search strategy was devised to ensure relevant literature could be identified, with the PECO framework being adopted to facilitate this and identify key search terms. As evidenced in this review, there is substantial data to support the hypothesis that heavy metals influence tumor development and progression. Unluckily the number of papers dealing with the determination of metals directly in samples from cancer tissues is still rather limited, so we decided to expand the scope of this review also to analyses carried out on other biological samples, as urine, plasma, hair, nail, etc. The studies reviewed showed that several limitations and current knowledge gaps are present in the literature that require further investigation to improve our comprehension of the impact of different heavy metals on tumorigenesis. Graphical abstract

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The Influence of Heavy Metals on Gastric Tumorigenesis

Cited by 8 publications

References 57 publications

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Quantitative distribution of essential elements and non-essential metals in breast cancer tissues by LA-ICP-TOF–MS

Heavy metals in biological samples of cancer patients: a systematic literature review

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The Influence of Heavy Metals on Gastric Tumorigenesis

Cited by 8 publications

References 57 publications

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N6-Methyladenosine Modification of ATP13A3

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N6-Methyladenosine Modification of ATP13A3

Quantitative distribution of essential elements and non-essential metals in breast cancer tissues by LA-ICP-TOF–MS

Heavy metals in biological samples of cancer patients: a systematic literature review

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Product

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Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3