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

被引：37

作者：

Sumardika, I. Wayan ^{[1
,2
]}

Chen, Youyi ^{[1
]}

Tomonobu, Nahoko ^{[1
]}

Kinoshita, Rie ^{[1
]}

Ruma, I. Made Winarsa ^{[1
,2
]}

Sato, Hiroki ^{[3
]}

Kondo, Eisaku ^{[4
]}

Inoue, Yusuke ^{[5
]}

Yamauchi, Akira ^{[6
]}

Murata, Hitoshi ^{[1
]}

Yamamoto, Ken-ichi ^{[1
]}

Tomida, Shuta ^{[7
]}

Shien, Kazuhiko ^{[3
]}

Yamamoto, Hiromasa ^{[3
]}

Soh, Junichi ^{[3
]}

Futami, Junichiro ^{[8
]}

Putranto, Endy Widya ^{[9
]}

Hibino, Toshihiko ^{[10
]}

Nishibori, Masahiro ^{[11
]}

Toyooka, Shinichi ^{[3
]}

Sakaguchi, Masakiyo ^{[1
]}

机构：

[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol, Okayama, Okayama, Japan

[2] Udayana Univ, Fac Med, Denpasar, Bali, Indonesia

[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Thorac Breast & Endocrinol Surg, Okayama, Okayama, Japan

[4] Niigata Univ, Grad Sch Med & Dent Sci, Div Mol & Cellular Pathol, Niigata, Niigata, Japan

[5] Gunma Univ, Div Mol Sci, Fac Sci & Technol, Kiryu, Gunma, Japan

[6] Kawasaki Med Sch, Dept Biochem, Kurashiki, Okayama, Japan

[7] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Biobank, Kita Ku, Okayama, Japan

[8] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med & Bioengn Sci, Kita Ku, Okayama, Japan

[9] Univ Gadjah Mada, Fac Med, Dr Sardjito Hosp, Dept Pediat, Yogyakarta, Indonesia

[10] Tokyo Med Univ, Dept Dermatol, Shinjuku Ku, Tokyo, Japan

[11] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pharmacol, Okayama, Okayama, Japan

来源：

MOLECULAR CARCINOGENESIS | 2019年 / 58卷 / 06期

关键词：

lung cancer; NFI; NPTN; S100; protein; S100A8; A9; SPDEF; NF-KAPPA-B; TRANSCRIPTION FACTOR; SUPPRESSOR-CELLS; PROTEINS S100A8; EXPRESSION; GENES; IDENTIFICATION; PATHWAYS; MELANOMA; RECEPTOR;

D O I：

10.1002/mc.22987

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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- (NPTN), 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 NPTN showed significantly high expression levels in lung cancer cell lines in a consistent manner. We hence aimed to determine the significance of NPTN as an S100A8/A9 receptor in lung cancer. Our results showed that NPTN 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 NPTN 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-NPTN 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.

引用

页码：980 / 995

页数：16

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