Reversing immune evasion in colon cancer

A newly discovered, naturally occurring compound, verticillin A, may provide long-awaited improvement in treating metastatic colon cancer.  Dr. Kebin Liu headed a study recently published in the Journal of Immunology, in which he and GRU Cancer Center researchers Amy Paschall and Drs. Jeong-Hyeon Choi, Wendy Bollag, and Asha Nayak-Kapoor and colleagues parsed the mechanism responsible for FAS silencing in colon cancer and propose a remedy to restore FAS-mediated cancer immune surveillance.  Through their studies, they demonstrate increased H3K9me3 in the FAS promoter of metastatic human colon cancer cells (tri-methylation of histone H3K9 is associated with transcriptional repression).  The Liu laboratory previously identified verticillin A as an anti-cancer agent in vitro and in vivo.  In the present study, the authors demonstrate that the histone methyltransferase activity of verticillin A directly targets H3K9me3 in the FAS promoter, resulting in restored Fas expression and subsequent reversal of immune evasion along with restoration of chemosensitivity, both in vitro and in vivo.  Based on their research, the authors suggest verticillin A as a promising agent in combination with TRAIL-based therapy and as a potentially safe and effective drug to target 5-FU-resistant colon cancer.

[Paschall AV, Yang D, Lu C, Choi JH, Li X, Liu F, Figueroa M, Oberlies NH, Pearce C, Bollag WB, Nayak-Kapoor A, Liu K. H3K9 trimethylation silences Fas expression to confer colon carcinoma immune escape and 5-fluorouracil chemoresistance. J Immunol. 2015 Aug 15; 195(4): 1868-82.]
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Allison Brown
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Written by Allison Brown

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