Novel role of ASC as a regulator of metastatic phenotype

Okada, Nagisa; Fujii, Chifumi; Matsumura, Tomohiro; Kitazawa, Masato; Taniguchi, Shun’ichiro; Hida, Shigeaki; Uhara, Hisashi; Okuyama, Ryuhei

doi:10.1016/j.jdermsci.2017.02.060

Cited by 2 publications

(4 citation statements)

References 41 publications

(59 reference statements)

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“…In agreement with this, as shown in our differential proteomics data, there was a two‐ to sixfold upregulation of TMS1, a card domain containing apoptosis‐associated protein. TMS1 is shown to be epigenetically silenced in many cancers and is associated with their tumorigenic potential . These observations support our phenotypic analysis.…”

Section: Discussionsupporting

confidence: 87%

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Depletion of keratin 8/18 modulates oncogenic potential by governing multiple signaling pathways

et al. 2018

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Section: Discussionsupporting

confidence: 87%

“…TMS1/ACS is known to be a potent regulator of TNF‐α‐mediated apoptosis and is epigenetically silenced during various malignancies . TMS1 was found to be upregulated in our quantitative proteomics data and further validated by western blot analysis (Fig.…”

Section: Resultssupporting

confidence: 60%

Depletion of keratin 8/18 modulates oncogenic potential by governing multiple signaling pathways

et al. 2018

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“…ROS levels, however, did not differ significantly between ASC knockdown and control cells. Interestingly, Src was constitutively activated in ASC-knockdown melanoma cells (Okada et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In order to clarify the mechanism of malignant phenotype procurement by ASC knockdown, we determined the phosphorylation levels of several molecules affecting cellular malignant phenotype that were reportedly induced by ASC suppression, including MAPK, NF-κB (Masumoto et al 2003;Hasegawa et al 2009;Liu et al 2013), and Src (Okada et al 2016). Src was constitutively phosphorylated in ASC knockdown cells as compared with controls ( Fig.…”

Section: Phosphorylated Src Is Upregulated In Asc-knockdown Cellsmentioning

confidence: 99%

Potential Role of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells

Sakaizawa

Matsumura

Fujii

et al. 2018

Tohoku J. Exp. Med.

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Primary lung cancer is the most frequent cause of cancer-related deaths worldwide. Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients failed to respond to cisplatin within several months, and the mechanisms underlying the cisplatin resistance have not been fully elucidated. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor protein in the formation of inflammasomes. ASC is also involved in apoptotic signaling. Importantly, ASC expression is decreased in lung cancer and various cancers, but its precise function in tumor progression remains unknown. To explore the hitherto unknown role of ASC in lung cancer, we initially searched for lung cancer cell lines with higher expression levels of ASC using Cancer Cell Line Encyclopedia (CCLE) database, thereby identifying the A549 human non-small cell lung cancer cell line. Accordingly, with retroviral shRNA, the expression of ASC was forced to decrease in A549 cells. Stable ASC-knockdown cells, thus established, showed the increased activities of proliferation, motility, and invasion, compared with control cells. Importantly, ASC-knockdown cells also became resistant to cisplatin, but not to other anti-cancer agents, 5-fluorouracil and paclitaxel. Bcl-2 and phospho-Src levels were increased in ASC-knockdown cells. A Bcl-2 inhibitor, ABT-199, induced an apoptotic response in ASC-knockdown cells, and dasatinib, a Src inhibitor, blocked cell invasiveness. Thus, ASC may be involved in tumor suppression and cell death via Bcl-2 and pSrc. Targeting Bcl-2 and Src in ASC-downregulated populations of lung cancer may improve treatment outcome.

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Novel role of ASC as a regulator of metastatic phenotype

Cited by 2 publications

References 41 publications

Depletion of keratin 8/18 modulates oncogenic potential by governing multiple signaling pathways

Depletion of keratin 8/18 modulates oncogenic potential by governing multiple signaling pathways

Potential Role of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells

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