NLRP1 Promotes Tumor Growth by Enhancing Inflammasome Activation and Suppressing Caspase-3 Activity in Human Melanoma

    May 2016 in “ Journal of Investigative Dermatology ”
    Zili Zhai, W. Liu, Yuchun Luo, Manjinder Kaur, Yiqun G. Shellman, David A. Norris, Charles A. Dinarello, Richard A. Spritz, Mayumi Fujita
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    TLDR NLRP1 helps melanoma tumors grow by boosting inflammasome activation and reducing caspase-3 activity.
    The 2016 study analyzed 216 melanoma tumor data and 13 human melanoma cell lines to investigate the role of NLRP1 in human melanoma. The researchers found that NLRP1, which is mainly expressed in the cytoplasm of melanoma cells, promotes tumor growth by enhancing inflammasome activation and suppressing caspase-3 activity. When NLRP1 was silenced in human metastatic melanoma cell lines, there was a reduction in caspase-1 activity, IL-1β production, IL-1β secretion, and NF-kB activity, indicating that NLRP1 inflammasome is active in metastatic melanoma. The study also suggested that NLRP1 suppresses caspase-3 activation via interaction with Apaf1 and caspase-9. This was the first study to reveal the tumor-promoting role of NLRP1 in cancer cells.
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