RRC ID 54923
著者 Chen Y, Sumardika IW, Tomonobu N, Winarsa Ruma IM, Kinoshita R, Kondo E, Inoue Y, Sato H, Yamauchi A, Murata H, Yamamoto KI, Tomida S, Shien K, Yamamoto H, Soh J, Liu M, Futami J, Sasai K, Katayama H, Kubo M, Putranto EW, Hibino T, Sun B, Nishibori M, Toyooka S, Sakaguchi M.
タイトル Melanoma cell adhesion molecule is the driving force behind the dissemination of melanoma upon S100A8/A9 binding in the original skin lesion.
ジャーナル Cancer Lett
Abstract Since metastasis accounts for the majority of cancer-associated deaths, studies on the mechanisms of metastasis are needed to establish innovative strategies for cancer treatment. We previously reported that melanoma cell adhesion molecule (MCAM) functions as a critical receptor for S100A8/A9, and binding of S100A8/A9 to MCAM results in the migration of melanoma cells to lung tissue. However, the critical role of MCAM in the original melanoma skin lesion is still not clear. In this study, we aimed to determine the importance of the S100A8/A9-MCAM axis in melanoma dissemination in a skin lesion as a critical early step for metastasis. Mechanistic studies revealed the downstream signaling of MCAM that signaled the induction of metastasis. S100A8/A9-MCAM binding activates mitogen-activated protein kinase kinase kinase 8 (MAP3K8), also termed TPL2, leading to strong activation of the transcription factor ETV4 and subsequent induction of matrix metalloproteinase-25 (MMP25), and finally to induction of melanoma lung tropic metastasis. Collectively, our results demonstrate a crucial role of the S100A8/A9-MCAM signaling axis in metastatic onset of melanoma cells and indicate that strategies targeting the identified pathway may be useful for the establishment of innovative anti-cancer therapies.
巻・号 452
ページ 178-190
公開日 2019-6-28
DOI 10.1016/j.canlet.2019.03.023
PII S0304-3835(19)30179-X
PMID 30904617
MeSH Animals CD146 Antigen / metabolism Calgranulin A / genetics Calgranulin A / metabolism* Calgranulin B / genetics Calgranulin B / metabolism* Cell Line, Tumor Cell Movement Cell Proliferation GPI-Linked Proteins / metabolism HEK293 Cells Humans Keratinocytes / pathology Lung Neoplasms / secondary MAP Kinase Kinase Kinases / metabolism Matrix Metalloproteinases, Membrane-Associated / metabolism Melanoma / pathology* Melanoma / therapy Melanoma, Experimental / pathology* Melanoma, Experimental / therapy Mice Mice, Inbred BALB C Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-ets / metabolism RNA Interference RNA, Small Interfering / genetics Skin / pathology Skin Neoplasms / pathology* Skin Neoplasms / therapy Xenograft Model Antitumor Assays
IF 6.508
引用数 6
リソース情報
ヒト・動物細胞 293T(RCB2202)