Clinical significance of apoptosis-associated speck-like protein containing a caspase recruitment domain in oral squamous cell carcinoma

Shimane, Tetsu; Kobayashi, H; Takeoka, Michiko; Kitazawa, Masato; Matsumura, Tomohiro; Hida, Shigeaki; Xiao, Tiepeng; Koike, Takeshi; Taniguchi, Shun’ichiro; Kitamura, Hiroshi

doi:10.1016/j.oooo.2013.03.013

Cited by 8 publications

(10 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, high level of ASC expression in OSCC specimens predicted poorer prognosis of patients, which is different from a previously report by Shimane et al [31]. The difference can be resulted from the following reasons.…”

Section: Discussioncontrasting

confidence: 99%

“…Of them, ASC was significantly correlated with various clinicopathological characteristics (Table 1), including node stage, overall stage [31], extracapsular spread, and perineural invasion, and was an independent predictor of OS, DSS, and DFS for OSCC patients (Table 2). In vitro and in vivo studies further demonstrated that ASC appears to promote tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ASC contributes to metastasis of oral cavity squamous cell carcinoma

Chang

OuYang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

ASC (Apoptosis-associated Speck-like protein containing a CARD) acts as a platform protein in the inflammasome cascade of some cancer types. However, its potential involvement in OSCC (oral cavity squamous cell carcinoma) has not yet been determined. Here, we investigated the potential role of ASC in OSCC. RT-qPCR analysis of 20 paired tumor and adjacent normal tissue samples revealed that the mRNA levels of ASC, along with IL-1β, CASP1, and NLRP3 in ASC-associated NLRP3 inflammasome were significantly elevated in OSCC tissues. Immunohistochemical staining of these four proteins in 111 clinical specimens revealed that high-level expression of ASC was significantly associated with tumor stage, node stage (p=0.001), overall stage (p<0.001), extracapsular spread (p<0.001), perineural invasion (p=0.004) and tumor depth (p<0.001). Kaplan-Meier survival analysis further revealed that high-level ASC expression was correlated with poorer overall survival (p=0.001), disease-specific survival (p<0.001) and disease-free survival (p<0.001). Studies using OSCC cell lines indicated that high-level ASC expression enhanced cell migration and invasion, and experiments using an orthotropic nude mouse model confirmed that ASC overexpression induced metastasis of OSCC cells. This is the first report to show that ASC contributes to OSCC metastasis, and that high-level ASC expression is a marker for poor prognosis in OSCC patients.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ASC contributes to metastasis of oral cavity squamous cell carcinoma

Chang

OuYang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…In lung cancer, diminished expression of ASC was correlated with the invasive stages of tumor progression, and the ASC promoter was significantly hypermethylated in invasive lung adenocarcinoma patients with metastasis to the lymph nodes [9]. Furthermore, our recent study indicated that ASC expression was significantly lower in nonborder invasive and diffusion type tissues than in noninvasive type tumors in OSCC [10]. Other groups have also identified relationships between silencing of the ASC gene by methylation and prognosis in prostate cancer [11,12], glioblastoma [13], hepatocellular carcinoma [14], cervical cancer [15], and others.…”

mentioning

confidence: 92%

“…We previously reported that ASC expression was reduced in melanoma [7], colorectal cancer [8], lung cancer [9], and oral squamous cell carcinoma (OSCC) [10]. In lung cancer, diminished expression of ASC was correlated with the invasive stages of tumor progression, and the ASC promoter was significantly hypermethylated in invasive lung adenocarcinoma patients with metastasis to the lymph nodes [9].…”

mentioning

confidence: 99%

Novel role of ASC as a regulator of metastatic phenotype

Okada

Fujii

Matsumura

et al. 2017

Journal of Dermatological Science

Self Cite

View full text Add to dashboard Cite

“…Concerning oral squamous cell carcinoma, one study (Shimane et al, 2013) found ASC highly expressed in normal oral mucosa, whereas expression was reduced in tumors as a function of the differentiation grade (well, moderately and poorly differentiated). ASC expression correlated with tumor site, T-classification, clinical stage, mode of invasion, histopathological differentiation, and lymphocytic infiltration.…”

Section: Asc Expression/aberrant Methylation and Clinical Outcomementioning

confidence: 99%

Dual Role of Inflammasome Adaptor ASC in Cancer

Protti

Monte

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Apoptosis-associated Speck-like protein containing a CARD (caspase activation and recruitment domain) (ASC), also called PYCARD/Target of Methylation-induced Silencing-1 (TMS1), was originally discovered as a protein that forms aggregates ("specks") in human leukemia cells treated with chemotherapeutic agents. Its expression was found to be silenced by methylation in many human tumors, preventing tumor cells from undergoing apoptosis and supporting its role as a tumor suppressor. Subsequently, ASC was also identified as a central adaptor molecule of the inflammasome complex, which mediates the secretion of inflammatory cytokines (i.e., IL-1β and IL-18). Inflammatory cytokines have been shown to mediate tumor-promoting functions. Thus, in the context of cancer development and progression, ASC may exert opposing functions, i.e., be either tumor-suppressing by inducing tumor cell apoptosis, or tumorpromoting by favoring secretion of inflammatory cytokines (by tumor cells and/or tumor infiltrating myeloid cells) within the tumor microenvironment. Here, we report and discuss this dual role of ASC by also considering the final contribution of each of its two main functions in several cancer types, taking into consideration the correlation between ASC expression, clinical correlates, and patients' survival. ASC and inflammasome targeting strategies are being developed. However, before the use of such treatments in clinical practice, it is fundamental to better dissect the role of ASC in different tumors, in order to privilege or avoid their use in those tumors in which ASC exerts an anti-tumor or pro-tumor function, respectively.

show abstract

Clinical significance of apoptosis-associated speck-like protein containing a caspase recruitment domain in oral squamous cell carcinoma

Cited by 8 publications

References 32 publications

ASC contributes to metastasis of oral cavity squamous cell carcinoma

ASC contributes to metastasis of oral cavity squamous cell carcinoma

Novel role of ASC as a regulator of metastatic phenotype

Dual Role of Inflammasome Adaptor ASC in Cancer

Contact Info

Product

Resources

About