TY - JOUR
T1 - NFAT5 promotes oral squamous cell carcinoma progression in a hyperosmotic environment
AU - Yoshimoto, Shohei
AU - Morita, Hiromitsu
AU - Matsuda, Miho
AU - Katakura, Yoshinori
AU - Hirata, Masato
AU - Hashimoto, Shuichi
N1 - Funding Information:
Acknowledgements This work was supported in part by Grants-in-Aid for Scientific Research (C) (18K07033 to SH), Grantin-Aid for Young Scientists (B) (17K18301 to SY) and Grants-in‐Aid for Young Scientists (20K18490 to SY) from Japan Society for the Promotion of Science (JSPS)/KAKENHI.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/1
Y1 - 2021/1
N2 - Epidermal growth factor receptor (EGFR) is highly expressed in several types of cancer cells including oral squamous cell carcinoma (OSCC). EGF/EGFR signaling is recognized as an important molecular target in cancer therapy. However, cancer cells often become tolerant to EGF/EGFR signaling-targeted therapies. In the tumor microenvironment, the tumor incites inflammation and the inflammation-derived cytokines make a considerable impact on cancer development. In addition, hyperosmolarity is also induced, but the role of osmotic stress in cancer development has not been fully understood. This study demonstrates molecular insights into hyperosmolarity effect on OSCC development and shows that NFAT5 transcription factor plays an important functional role in enhancing the oral cancer cell proliferation by inducing the EGFR translocation from the endoplasmic reticulum to the plasma membrane through increase the expression of DPAGT1, an essential enzyme for catalyzing the first committed step of N-linked protein glycosylation. These results suggest that hyperosmolarity-induced intra-nuclear translocation of NFAT5 essential for DPAGT1 activation and EGFR subcellular translocation responsible for OSCC tumor progression.
AB - Epidermal growth factor receptor (EGFR) is highly expressed in several types of cancer cells including oral squamous cell carcinoma (OSCC). EGF/EGFR signaling is recognized as an important molecular target in cancer therapy. However, cancer cells often become tolerant to EGF/EGFR signaling-targeted therapies. In the tumor microenvironment, the tumor incites inflammation and the inflammation-derived cytokines make a considerable impact on cancer development. In addition, hyperosmolarity is also induced, but the role of osmotic stress in cancer development has not been fully understood. This study demonstrates molecular insights into hyperosmolarity effect on OSCC development and shows that NFAT5 transcription factor plays an important functional role in enhancing the oral cancer cell proliferation by inducing the EGFR translocation from the endoplasmic reticulum to the plasma membrane through increase the expression of DPAGT1, an essential enzyme for catalyzing the first committed step of N-linked protein glycosylation. These results suggest that hyperosmolarity-induced intra-nuclear translocation of NFAT5 essential for DPAGT1 activation and EGFR subcellular translocation responsible for OSCC tumor progression.
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U2 - 10.1038/s41374-020-00486-1
DO - 10.1038/s41374-020-00486-1
M3 - Article
C2 - 32901097
AN - SCOPUS:85090475259
SN - 0023-6837
VL - 101
SP - 38
EP - 50
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 1
ER -
