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 language | English |
|---|---|
| Journal | Molecular Carcinogenesis |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Neuroplastin-β mediates S100A8/A9-induced lung cancer disseminative progression
AU - Sumardika, I. Wayan
AU - Chen, Youyi
AU - Tomonobu, Nahoko
AU - Kinoshita, Rie
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
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - lung cancer
KW - NFI
KW - NPTNβ
KW - S100 protein
KW - S100A8/A9
KW - SPDEF
UR - http://www.scopus.com/inward/record.url?scp=85062328099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062328099&partnerID=8YFLogxK
U2 - 10.1002/mc.22987
DO - 10.1002/mc.22987
M3 - Article
C2 - 30720226
AN - SCOPUS:85062328099
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
ER -