Neuroplastin-β mediates S100A8/A9-induced lung cancer disseminative progression

I. Wayan Sumardika, Youyi Chen, Nahoko Tomonobu, Rie Kinoshita, I. Made Winarsa Ruma, Hiroki Sato, Eisaku Kondo, Yusuke Inoue, Akira Yamauchi, Hitoshi Murata, Ken-ichi Yamamoto, Shuta Tomida, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Sou, Junichiro Futami, Endy Widya Putranto, Toshihiko Hibino, Masahiro Nishibori, Shinichi ToyookaMasakiyo Sakaguchi

Research output: Contribution to journalArticle

Abstract

Compiling evidence indicates an unusual role of extracellular S100A8/A9 in cancer metastasis. S100A8/A9 secreted from either cancer cells or normal cells including epithelial and inflammatory cells stimulates cancer cells through S100A8/A9 sensor receptors in an autocrine or paracrine manner, leading to cancer cell metastatic progression. We previously reported a novel S100A8/A9 receptor, neuroplastin-β (NPTNβ), which plays a critical role in atopic dermatitis when it is highly activated in keratinocytes by an excess amount of extracellular S100A8/A9 in the inflammatory skin lesion. Interestingly, our expression profiling of NPTNβ showed significantly high expression levels in lung cancer cell lines in a consistent manner. We hence aimed to determine the significance of NPTNβ as an S100A8/A9 receptor in lung cancer. Our results showed that NPTNβ has strong ability to induce cancer-related cellular events, including anchorage-independent growth, motility and invasiveness, in lung cancer cells in response to extracellular S100A8/A9, eventually leading to the expression of a cancer disseminative phenotype in lung tissue in vivo. Mechanistic investigation revealed that binding of S100A8/A9 to NPTNβ mediates activation of NFIA and NFIB and following SPDEF transcription factors through orchestrated upstream signals from TRAF2 and RAS, which is linked to anchorage-independent growth, motility and invasiveness. Overall, our results indicate the importance of the S100A8/A9-NPTNβ axis in lung cancer disseminative progression and reveal a pivotal role of its newly identified downstream signaling, TRAF2/RAS-NFIA/NFIB-SPDEF, in linking to the aggressive development of lung cancers.

Original languageEnglish
JournalMolecular Carcinogenesis
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Lung Neoplasms
TNF Receptor-Associated Factor 2
Neoplasms
Atopic Dermatitis
Growth
Keratinocytes
Transcription Factors
Epithelial Cells
Neoplasm Metastasis
Phenotype
Cell Line
Lung
Skin

Keywords

  • lung cancer
  • NFI
  • NPTNβ
  • S100 protein
  • S100A8/A9
  • SPDEF

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Neuroplastin-β mediates S100A8/A9-induced lung cancer disseminative progression. / Sumardika, I. Wayan; Chen, Youyi; Tomonobu, Nahoko; Kinoshita, Rie; Ruma, I. Made Winarsa; Sato, Hiroki; Kondo, Eisaku; Inoue, Yusuke; Yamauchi, Akira; Murata, Hitoshi; Yamamoto, Ken-ichi; Tomida, Shuta; Shien, Kazuhiko; Yamamoto, Hiromasa; Sou, Junichi; Futami, Junichiro; Putranto, Endy Widya; Hibino, Toshihiko; Nishibori, Masahiro; Toyooka, Shinichi; Sakaguchi, Masakiyo.

In: Molecular Carcinogenesis, 01.01.2019.

Research output: Contribution to journalArticle

Sumardika, I. Wayan ; Chen, Youyi ; Tomonobu, Nahoko ; Kinoshita, Rie ; Ruma, I. Made Winarsa ; Sato, Hiroki ; Kondo, Eisaku ; Inoue, Yusuke ; Yamauchi, Akira ; Murata, Hitoshi ; Yamamoto, Ken-ichi ; Tomida, Shuta ; Shien, Kazuhiko ; Yamamoto, Hiromasa ; Sou, Junichi ; Futami, Junichiro ; Putranto, Endy Widya ; Hibino, Toshihiko ; Nishibori, Masahiro ; Toyooka, Shinichi ; Sakaguchi, Masakiyo. / Neuroplastin-β mediates S100A8/A9-induced lung cancer disseminative progression. In: Molecular Carcinogenesis. 2019.
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AU - Ruma, I. Made Winarsa

AU - Sato, Hiroki

AU - Kondo, Eisaku

AU - Inoue, Yusuke

AU - Yamauchi, Akira

AU - Murata, Hitoshi

AU - Yamamoto, Ken-ichi

AU - Tomida, Shuta

AU - Shien, Kazuhiko

AU - Yamamoto, Hiromasa

AU - Sou, Junichi

AU - Futami, Junichiro

AU - Putranto, Endy Widya

AU - Hibino, Toshihiko

AU - Nishibori, Masahiro

AU - Toyooka, Shinichi

AU - Sakaguchi, Masakiyo

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