TY - JOUR
T1 - Neuroplastinβ-mediated upregulation of solute carrier family 22 member 18 antisense (SLC22A18AS) plays a crucial role in the epithelial-mesenchymal transition, leading to lung cancer cells' enhanced motility
AU - Bajkowska, Karolina
AU - Sumardika, I. Wayan
AU - Tomonobu, Nahoko
AU - Chen, Youyi
AU - Yamamoto, Ken ichi
AU - Kinoshita, Rie
AU - Murata, Hitoshi
AU - Gede Yoni Komalasari, Ni Luh
AU - Jiang, Fan
AU - Yamauchi, Akira
AU - Winarsa Ruma, I. Made
AU - Kasano-Camones, Carlos Ichiro
AU - Inoue, Yusuke
AU - Sakaguchi, Masakiyo
N1 - Funding Information:
This research was supported in part by a grant from the JSPS KAKENHI (no. 17H03577 to M.S.) and by funds to M.S. from the Smoking Research Foundation , the Terumo Life Science Foundation, and the Takeda Science Foundation .
Publisher Copyright:
© 2020 The Authors
PY - 2020/7
Y1 - 2020/7
N2 - Our recent study revealed an important role of the neuroplastin (NPTN)β downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTNβ is a serial activation of the key molecules we identified: tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF). The question of how dissemination is controlled by SPDEF under the activated NPTNβ has not been answered. Here, we show that the NPTNβ-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTNβ pathway in lung cancer cells. In vitro, the induced EMT is linked to the acquisition of active cellular motility but not growth, and this is correlated with highly disseminative tumor progression in vivo. The publicly available data also show the poor survival of SLC22A18AS-overexpressing lung cancer patients. Taken together, these data highlight a crucial role of SLC22A18AS in lung cancer dissemination, which provides novel input of this molecule to the signal cascade of NPTNβ. Our findings contribute to a better understanding of NPTNβ-mediated lung cancer metastasis.
AB - Our recent study revealed an important role of the neuroplastin (NPTN)β downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTNβ is a serial activation of the key molecules we identified: tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF). The question of how dissemination is controlled by SPDEF under the activated NPTNβ has not been answered. Here, we show that the NPTNβ-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTNβ pathway in lung cancer cells. In vitro, the induced EMT is linked to the acquisition of active cellular motility but not growth, and this is correlated with highly disseminative tumor progression in vivo. The publicly available data also show the poor survival of SLC22A18AS-overexpressing lung cancer patients. Taken together, these data highlight a crucial role of SLC22A18AS in lung cancer dissemination, which provides novel input of this molecule to the signal cascade of NPTNβ. Our findings contribute to a better understanding of NPTNβ-mediated lung cancer metastasis.
KW - Epithelial-mesenchymal transition
KW - Lung cancer
KW - Metastasis
KW - Neuroplastin
KW - S100A8/A9
KW - Solute carrier family 22 member 18 antisense
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U2 - 10.1016/j.bbrep.2020.100768
DO - 10.1016/j.bbrep.2020.100768
M3 - Article
AN - SCOPUS:85084553985
VL - 22
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
SN - 2405-5808
M1 - 100768
ER -