Absent in melanoma 2 proteins in the development of cancer

Choubey, Divaker

doi:10.1007/s00018-016-2296-9

Cited by 29 publications

(27 citation statements)

References 73 publications

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“…AIM2 is a member of the interferon‐inducible PYHIN (PYRIN and HIN domain‐containing) family proteins (also known as p200‐family proteins) and serves as the front line of defense against pathogen infection via caspase‐1 activation (Chuong et al ., 2016; Gray et al ., 2016; Man and Kanneganti, 2015; Rommereim and Subramanian, 2015). Aberration of AIM2 results in a large number of diseases (Choubey, 2016; Man et al ., 2015). Previous studies have shown that AIM2 was differently expressed and functioned as both a tumor suppressor and oncogene in human cancers.…”

Section: Introductionmentioning

confidence: 99%

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Chen

Liu

et al. 2017

Molecular Oncology

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Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma (HCC). Absent in melanoma 2 (AIM2) has been implicated in inflammation and carcinogenesis, although its role in HCC metastasis remains unknown. In the present study, we show that AIM2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds. In vitro studies demonstrated that AIM2 expression was modulated by hepatitis B virus X protein (HBx) at transcriptional and post‐translational levels. HBx overexpression markedly blocked the expression of AIM2 at mRNA and protein levels by enhancing the stability of Enhancer of zeste homolog 2 (EZH2). Furthermore, HBx interacted with AIM2, resulting in an increase of AIM2 degradation via ubiquitination induction. Functionally, knockdown of AIM2 enhanced cell migration, formation of cell pseudopodium, wound healing and tumor metastasis, whereas reintroduction of AIM2 attenuated these functions. The loss of AIM2 induced the activation of epithelial‐mesenchymal transition (EMT). Fibronectin 1 (FN1) was found to be a downstream effector of AIM2, with its expression reversely modulated by AIM2. Silencing of FN1 significantly halted cell migration induced by AIM2 depletion. These data demonstrate that HBx‐induced loss of AIM2 is associated with poor outcomes and facilitates HCC metastasis by triggering the EMT process. The results of the present study therefore suggest that AIM2 is a potential prognostic biomarker in hepatitis B virus‐related HCC, as well as a possible therapeutic target for tumor metastasis.

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Section: Introductionmentioning

confidence: 99%

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Chen

Liu

et al. 2017

Molecular Oncology

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“…The function of AIM2 is also highly controlled by regulation of its expression and subcellular localization that may vary depending on several factors including the activation of other DNA sensors, the overall inflammatory status, and the tissues involved. Moreover the contribution of AIM2 regulators such as POP3, p202, and TRIM11 are still poorly understood and need to be evaluated in physiological models . It would be important to understand the contribution of these regulators to the modulation of the intensity and duration of the response as well as their possible role as safeguard mechanisms limiting aberrant detection of self‐DNA.…”

Section: Discussionmentioning

confidence: 99%

“…AIM2 was found overexpressed following reversion of the tumorigenic phenotype by introduction of human chromosome 6 in UACC‐903. Downregulation of AIM2 protein expression was shown to play an important role in colorectal cancers that display mutations in AIM2 gene, silencing by DNA hypermethylation, and specific decreased tumor tissue expression . Similarly, prostate cancer cells also show decreased AIM2 expression compared to cells from healthy prostate and begnin prostate hyperplasia samples .…”

Section: Aim2 In Health and Diseasementioning

confidence: 99%

“…Chronic inflammation promoted by environment, microbial organisms, or microbiota is a major driver of cancer. 153 155 that display mutations in AIM2 gene, 156 silencing by DNA hypermethylation, 157 and specific decreased tumor tissue expression. 158 Similarly, prostate cancer cells also show decreased AIM2 expression compared to cells from healthy prostate and begnin prostate hyperplasia samples.…”

Section: Cancermentioning

confidence: 99%

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The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Lugrin

Martinon

2017

Immunological Reviews

261

182

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Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. This triggers the maturation and secretion of the cytokines IL-1β and IL-18. It can also initiate pyroptosis, a proinflammatory form of cell death. The AIM2 inflammasome contributes to physiological responses and diseases. It is a key player in host defenses, but its deregulation can contribute immune-linked diseases, such as autoinflammatory and autoimmune pathologies. Moreover, AIM2 may play a role in cancer development. Recent studies have shown that the detection of self-DNA species by AIM2 is an important factor that contributes to diseases associated with perturbation of cellular homeostasis. Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity.

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“…Although NLRP3 and NLRC4 inflammasomes are involved in carcinogenesis and anticancer immune responses 11 , AIM2 inflammasome has not been reported to induce cancer development. Instead of inflammasome activation, loss of AIM22 gene has been shown to result in cancer growth while mutation of AIM2 is associated with development of various cancers in humans 31, 32 . Moreover, Aim2 −/− mice showed increased size and number of colon tumors in a colitis-associated cancer (CAC) model, implying that the AIM2 gene itself regulates tumor progress and prevents colorectal cancer 33 .…”

Section: Discussionmentioning

confidence: 99%

Lentinan from shiitake selectively attenuates AIM2 and non-canonical inflammasome activation while inducing pro-inflammatory cytokine production

Ahn

Jeon

Kim

et al. 2017

Sci Rep

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Lentinan extracted from shiitake (Lentinula edodes) is a β-glucan that has been reported as an intravenous anti-tumor polysaccharide via enhancement of the host immune system. In this study, we determined the effect of lentinan on inflammasome activation, a multi-protein platform, in myeloid cells. Mouse bone marrow-derived macrophages were treated with lentinan with/without inflammasome triggers, and maturation of interleukin (IL)-1β, IL-18, or caspase-1 was measured as a readout of inflammasome activation. As a result, lentinan selectively inhibited absent in melanoma 2 (AIM2) inflammasome activation. In addition, lentinan up-regulated pro-inflammatory cytokines and induced expression of inflammasome-related genes through toll-like receptor 4 signaling. Furthermore, we assessed the effect of lentinan on mice treated with Listeria monocytogenes or lipopolysaccharide as an AIM2 or non-canonical inflammasome-mediated model. Lentinan attenuated IL-1β secretion resulting from Listeria-mediated AIM2 inflammasome activation and reduced endotoxin lethality via inhibition of non-canonical inflammasome activation. Thus, lentinan is suggested as an anti-AIM2 and anti-non-canonical inflammasome candidate despite its up-regulation of cytokine expression.

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Absent in melanoma 2 proteins in the development of cancer

Cited by 29 publications

References 73 publications

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Lentinan from shiitake selectively attenuates AIM2 and non-canonical inflammasome activation while inducing pro-inflammatory cytokine production

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