K15 Promoter-Driven Enforced Expression of NKIRAS Exhibits Tumor Suppressive Activity Against the Development of DMBA/TPA-Induced Skin Tumors

    October 2021 in “ Scientific Reports ”
    Kenji Tago, Satoshi Ohta, Chihiro Aoki‐Ohmura, Megumi Funakoshi‐Tago, Miho Sashikawa, Takeshi Matsui, Yuki Miyamoto, Taeko Wada, Tomoyuki Oshio, Mayumi Komine, Jitsuhiro Matsugi, Yusuke Furukawa, Mamitaro Ohtsuki, Junji Yamauchi, Ken Yanagisawa
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    Studysummary This study found that NKIRAS2 expression affects skin tumor suppression and HRAS-driven transformation in mice, indicating its role in carcinogenesis depends on expression level and cellular context. Our plain-language summary of this paper — not a Tressless recommendation.
    The study investigated the role of NKIRAS2 in carcinogenesis using transgenic mice with enforced expression of NKIRAS2 driven by a K15 promoter, primarily active in follicle bulge cells. The results showed that NKIRAS2 expression did not affect epidermal development but effectively suppressed DMBA/TPA-induced skin tumors, indicating a tumor suppressive role in follicle bulges. However, in murine fibroblasts, NKIRAS2 was necessary for HRAS-mutant-driven cellular transformation, with moderate expression enhancing and excessive expression suppressing oncogenic activity. This suggested that NKIRAS2's role in cancer is influenced by cellular context and expression level, exhibiting a biphasic effect on HRAS-driven oncogenesis.
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