Absent in melanoma 2 suppresses epithelial‐mesenchymal transition via Akt and inflammasome pathways in human colorectal cancer cells

Yang, Yunjia; Zhang, Minda; Jin, Chenyu; Ding, Yang; Yang, Mei; Wang, Rui; Zhou, Yunjiang; Zhou, Yang; Li, Tao; Wang, Keke; Hu, Rong

doi:10.1002/jcb.29040

Cited by 8 publications

(6 citation statements)

References 54 publications

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“…Previous study showed that Akt is a pivotal serine/threonine kinase and promotes epithelial‐mesenchymal transition process through NF‐κB and GSK‐3β in cell biological progression including cell proliferation, apoptosis and metabolism. AIM2 inflammasome activation impaired cell invasion and metastasis via inhibiting Akt pathway in colorectal cancer 33 . Furthermore, overexpression of AIM2 in human renal cancer suppressed cell metastasis via enhancing autophagy induction 21 .…”

Section: Discussionmentioning

confidence: 95%

“…AIM2 inflammasome activation impaired cell invasion and metastasis via inhibiting Akt pathway in colorectal cancer. 33 Furthermore, overexpression of AIM2 in human renal cancer suppressed cell metastasis via enhancing autophagy induction. 21 Our results indicated that inflammasome inhibitor YVAD-CMK resulted in the reduction of oncolytic effect by Ad-CAIX promotor -AIM2, implied that this efficiency was dependent on AIM2 inflammasome activation responses.…”

Section: Ad-caix Promotor -Aim2 Promoted the Inhibition Of Lung Metas...mentioning

confidence: 99%

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Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Chai

Qin

Zhang

et al. 2020

J Cellular Molecular Medi

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Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIXpromotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIXpromotor‐AIM2 adenoviruses (Ad‐CAIXpromotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIXpromotor, Ad‐CAIXpromotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIXpromotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIXpromotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIXpromotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIXpromotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.

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Section: Discussionmentioning

confidence: 95%

Section: Ad-caix Promotor -Aim2 Promoted the Inhibition Of Lung Metas...mentioning

confidence: 99%

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Chai

Qin

Zhang

et al. 2020

J Cellular Molecular Medi

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“…No phosphorylation sites responsible for regulating the activity of either AIM2 or NLRP1 have been characterised, although several putative sites have been identified in high-throughput screens according to PhosphoSitePlus® [72]. Interestingly, AIM2 has inflammasome-independent roles in mouse models of colon cancer and in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of multiple sclerosis [73][74][75]. In cancerous colonic epithelial cells AIM2 binds and inactivates the kinase DNA-PK, which is needed for AKT activation and regulates colon cancer progression [73].…”

Section: Aim2 and Nlrp1mentioning

confidence: 99%

PHOrming the inflammasome: phosphorylation is a critical switch in inflammasome signalling

McKee

Fischer

Bezbradica

et al. 2021

Biochemical Society Transactions

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Inflammasomes are protein complexes in the innate immune system that regulate the production of pro-inflammatory cytokines and inflammatory cell death. Inflammasome activation and subsequent cell death often occur within minutes to an hour, so the pathway must be dynamically controlled to prevent excessive inflammation and the development of inflammatory diseases. Phosphorylation is a fundamental post-translational modification that allows rapid control over protein function and the phosphorylation of inflammasome proteins has emerged as a key regulatory step in inflammasome activation. Phosphorylation of inflammasome sensor and adapter proteins regulates their inter- and intra-molecular interactions, subcellular localisation, and function. The control of inflammasome phosphorylation may thus provide a new strategy for the development of anti-inflammatory therapeutics. Herein we describe the current knowledge of how phosphorylation operates as a critical switch for inflammasome signalling.

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“…The absence of PI3K/Akt pathway suppression by AIM2 has been shown to decrease apoptosis in HCT116 CRC cells [ 48 ], as well as increase the capacity of stem cells to form organoids in culture [ 45 ]. However, other studies have suggested that AIM2 may regulate CRC via caspase-1-mediated induction of cell death and regulation of the epithelial-to-mesenchymal transition [ 49 , 50 ].…”

Section: Nlr Family Apoptosis Inhibitory Proteinsmentioning

confidence: 99%

Inflammasome-independent functions of NAIPs and NLRs in the intestinal epithelium

Scarfe

Mackie

Maslowski

2021

Biochemical Society Transactions

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The gut relies on the complex interaction between epithelial, stromal and immune cells to maintain gut health in the face of food particles and pathogens. Innate sensing by the intestinal epithelium is critical for maintaining epithelial barrier function and also orchestrating mucosal immune responses. Numerous innate pattern recognition receptors (PRRs) are involved in such sensing. In recent years, several Nucleotide-binding-domain and Leucine-rich repeat-containing receptors (NLRs) have been found to partake in pathogen or damage sensing while also being implicated in gut pathologies, such as colitis and colorectal cancer (CRC). Here, we discuss the current literature focusing on NLR family apoptosis inhibitory proteins (NAIPs) and other NLRs that have non-inflammasome roles in the gut. The mechanisms behind NLR-mediated protection often converges on similar signalling pathways, such as STAT3, MAPK and NFκB. Further understanding of how these NLRs contribute to the maintenance of gut homeostasis will be important for understanding gut pathologies and developing new therapies.

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Absent in melanoma 2 suppresses epithelial‐mesenchymal transition via Akt and inflammasome pathways in human colorectal cancer cells

Cited by 8 publications

References 54 publications

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

PHOrming the inflammasome: phosphorylation is a critical switch in inflammasome signalling

Inflammasome-independent functions of NAIPs and NLRs in the intestinal epithelium

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