Dual Role of Inflammasome Adaptor ASC in Cancer
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 chemotherapeu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00040/full |
| _version_ | 1818549487024472064 |
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| author | Maria Pia Protti Maria Pia Protti Lucia De Monte Lucia De Monte |
| author_facet | Maria Pia Protti Maria Pia Protti Lucia De Monte Lucia De Monte |
| author_sort | Maria Pia Protti |
| collection | DOAJ |
| description | 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 tumor-promoting 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. |
| first_indexed | 2024-12-12T08:33:58Z |
| format | Article |
| id | doaj.art-5f3c123021a44a688728e5063c57acfc |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T08:33:58Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-5f3c123021a44a688728e5063c57acfc2022-12-22T00:30:59ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-02-01810.3389/fcell.2020.00040521272Dual Role of Inflammasome Adaptor ASC in CancerMaria Pia Protti0Maria Pia Protti1Lucia De Monte2Lucia De Monte3Tumor Immunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, ItalyDivision of Immunology, Transplantation and Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, ItalyTumor Immunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, ItalyDivision of Immunology, Transplantation and Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, ItalyApoptosis-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 tumor-promoting 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.https://www.frontiersin.org/article/10.3389/fcell.2020.00040/fullASC/TMS1tumor cellsmyeloid cellstumor suppressor geneinflammasomeIL1 |
| spellingShingle | Maria Pia Protti Maria Pia Protti Lucia De Monte Lucia De Monte Dual Role of Inflammasome Adaptor ASC in Cancer Frontiers in Cell and Developmental Biology ASC/TMS1 tumor cells myeloid cells tumor suppressor gene inflammasome IL1 |
| title | Dual Role of Inflammasome Adaptor ASC in Cancer |
| title_full | Dual Role of Inflammasome Adaptor ASC in Cancer |
| title_fullStr | Dual Role of Inflammasome Adaptor ASC in Cancer |
| title_full_unstemmed | Dual Role of Inflammasome Adaptor ASC in Cancer |
| title_short | Dual Role of Inflammasome Adaptor ASC in Cancer |
| title_sort | dual role of inflammasome adaptor asc in cancer |
| topic | ASC/TMS1 tumor cells myeloid cells tumor suppressor gene inflammasome IL1 |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00040/full |
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