Melanoma cell adhesion molecule is the driving force behind the dissemination of melanoma upon S100A8/A9 binding in the original skin lesion

Youyi Chen, I. Wayan Sumardika, Nahoko Tomonobu, I. Made Winarsa Ruma, Rie Kinoshita, Eisaku Kondo, Yusuke Inoue, Hiroki Sato, Akira Yamauchi, Hitoshi Murata, Ken-ichi Yamamoto, Shuta Tomida, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Sou, Ming Liu, Junichiro Futami, Kaori Sasai, Hiroshi Katayama, Miyoko KuboEndy Widya Putranto, Toshihiko Hibino, Bei Sun, Masahiro Nishibori, Shinichi Toyooka, Masakiyo Sakaguchi

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)178-190
Number of pages13
JournalCancer Letters
Volume452
DOIs
Publication statusPublished - Jun 28 2019

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CD146 Antigens
Melanoma
Skin
Neoplasm Metastasis
MAP Kinase Kinase Kinases
Neoplasms
Lung
Cell Movement
Transcription Factors

Keywords

  • Inflammation
  • Matrix metalloproteinase
  • Metastasis
  • S100 protein
  • Seed and soil hypothesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Melanoma cell adhesion molecule is the driving force behind the dissemination of melanoma upon S100A8/A9 binding in the original skin lesion. / Chen, Youyi; Sumardika, I. Wayan; Tomonobu, Nahoko; Winarsa Ruma, I. Made; Kinoshita, Rie; Kondo, Eisaku; Inoue, Yusuke; Sato, Hiroki; Yamauchi, Akira; Murata, Hitoshi; Yamamoto, Ken-ichi; Tomida, Shuta; Shien, Kazuhiko; Yamamoto, Hiromasa; Sou, Junichi; Liu, Ming; Futami, Junichiro; Sasai, Kaori; Katayama, Hiroshi; Kubo, Miyoko; Putranto, Endy Widya; Hibino, Toshihiko; Sun, Bei; Nishibori, Masahiro; Toyooka, Shinichi; Sakaguchi, Masakiyo.

In: Cancer Letters, Vol. 452, 28.06.2019, p. 178-190.

Research output: Contribution to journalArticle

Chen, Youyi ; Sumardika, I. Wayan ; Tomonobu, Nahoko ; Winarsa Ruma, I. Made ; Kinoshita, Rie ; Kondo, Eisaku ; Inoue, Yusuke ; Sato, Hiroki ; Yamauchi, Akira ; Murata, Hitoshi ; Yamamoto, Ken-ichi ; Tomida, Shuta ; Shien, Kazuhiko ; Yamamoto, Hiromasa ; Sou, Junichi ; Liu, Ming ; Futami, Junichiro ; Sasai, Kaori ; Katayama, Hiroshi ; Kubo, Miyoko ; Putranto, Endy Widya ; Hibino, Toshihiko ; Sun, Bei ; Nishibori, Masahiro ; Toyooka, Shinichi ; Sakaguchi, Masakiyo. / Melanoma cell adhesion molecule is the driving force behind the dissemination of melanoma upon S100A8/A9 binding in the original skin lesion. In: Cancer Letters. 2019 ; Vol. 452. pp. 178-190.
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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.",
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AU - Chen, Youyi

AU - Sumardika, I. Wayan

AU - Tomonobu, Nahoko

AU - Winarsa Ruma, I. Made

AU - Kinoshita, Rie

AU - Kondo, Eisaku

AU - Inoue, Yusuke

AU - Sato, Hiroki

AU - Yamauchi, Akira

AU - Murata, Hitoshi

AU - Yamamoto, Ken-ichi

AU - Tomida, Shuta

AU - Shien, Kazuhiko

AU - Yamamoto, Hiromasa

AU - Sou, Junichi

AU - Liu, Ming

AU - Futami, Junichiro

AU - Sasai, Kaori

AU - Katayama, Hiroshi

AU - Kubo, Miyoko

AU - Putranto, Endy Widya

AU - Hibino, Toshihiko

AU - Sun, Bei

AU - Nishibori, Masahiro

AU - Toyooka, Shinichi

AU - Sakaguchi, Masakiyo

PY - 2019/6/28

Y1 - 2019/6/28

N2 - 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.

AB - 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.

KW - Inflammation

KW - Matrix metalloproteinase

KW - Metastasis

KW - S100 protein

KW - Seed and soil hypothesis

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