フルテキストURL Mol_Cell_Biol_28_7_2391.pdf
著者 Eguchi, Takanori| Kubota, Satoshi| Kawata, Kazumi| Mukudai, Yoshiki| Uehara, Junji| Ohgawara, Toshihiro| Ibaragi, Soichiro| Sasaki, Akira| Kuboki, Takuo| Takigawa, Masaharu|
抄録  Matrix metalloproteinase 3 (MMP3) is well known as a secretory endopeptidase that degrades extracellular matrices. Recent reports indicated the presence of MMPs in the nucleus (A. J. Kwon et al., FASEB J. 18:690-692, 2004); however, its function has not been well investigated. Here, we report a novel function of human nuclear MMP3 as a trans regulator of connective tissue growth factor (CCN2/CTGF). Initially, we cloned MMP3 cDNA as a DNA-binding factor for the CCN2/CTGF gene. An interaction between MMP3 and transcription enhancer dominant in chondrocytes (TRENDIC) in the CCN2/CTGF promoter was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by overexpressed MMP3, whereas a TRENDIC mutant promoter lost the response. Also, the knocking down of MMP3 suppressed CCN2/CTGF expression. By cytochemical and histochemical analyses, MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 and six putative nuclear localization signals in MMP3 also were shown. Furthermore, we determined that heterochromatin protein gamma coordinately regulates CCN2/CTGF by interacting with MMP3. The involvement of this novel role of MMP3 in the development, tissue remodeling, and pathology of arthritic diseases through CCN2/CTGF regulation thus is suggested.
発行日 2008-04
出版物タイトル Molecular and Cellular Biology
28巻
7号
出版者 American Society for Microbiology
開始ページ 2391
終了ページ 2413
ISSN 0270-7306
NCID AA10620925
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
論文のバージョン publisher
PubMed ID 18172013
DOI 10.1128/MCB.01288-07
Web of Sience KeyUT 000254181400025
関連URL isVersionOf https://doi.org/10.1128/MCB.01288-07
フルテキストURL Biochem_Biophy_Res_Comm_201807.pdf
著者 Fujiwara, Toshifumi| Eguchi, Takanori| Sogawa, Chiharu| Ono, Kisho| Murakami, Jun| Ibaragi, Soichiro| Asaumi, Jun-ichi| Okamoto, Kuniaki| Calderwood, Stuart K.| Kozaki, Ken-ichi|
抄録 Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.
キーワード Extracellular vesicles Anti-EGFR antibody therapy Cetuximab Epithelial-to-mesenchymal transition Head and neck squamous cell carcinoma
発行日 2018-07-13
出版物タイトル Biochemical and Biophysical Research Communications A
出版者 Elsevier
ISSN 0006291X
NCID AA00564395
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
著作権者 http://creativecommons.org/licenses/by-nc-nd/4.0/
論文のバージョン publisher
DOI 10.1016/j.bbrc.2018.07.035
関連URL isVersionOf https://doi.org/10.1016/j.bbrc.2018.07.035