title: High-mobility group box 1 (HMGB1) protein regulates tumor-associated cell migration through the interaction with BTB domain.
abstract: High-mobility group box 1 (HMGB1) was shown to be strongly implicated in high incidences of metastasis and the poor clinical pathologic conditions found in various human tumors. In this study, we explored the possible mechanism of HMGB1 in tumor metastases in vitro, using a human carcinoma cell system. BTB, as a negative regulator of cell cycle progression, was identified as a HMGB1 interacting partner. The ectopic expression of HMGB1 activates cell growth by suppressing BTB-induced cell death, decreasing Bax and p53 expression, while enhancing Bcl-xL, Bcl-2, cyclin D1, and NF-κB expression. HMGB1 activates the FAK/PI3K/mTOR signaling cascade, and BTB prominently inhibits HMGB1-induced oncogenesis. The effect of HMGB1 on FAK/mTOR signaling was also confirmed through the silencing of HMGB1 expression. These insights provide evidence that HMGB1 enhances cell proliferation and suppresses apoptosis. Collectively, our results show an underlying mechanism for an HMGB1-associated promotion of carcinoma cells.
authors.affiliation: Department of Obstetrics and Gynecology, Chungnam National University Hospital, 282, Munhwa-ro, Jung-gu, Daejeon 301-721, Republic of Korea.
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Ko
authors.affiliation: Research Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Boh-Ram
authors.initials: BR
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Chungnam National University Hospital, 282, Munhwa-ro, Jung-gu, Daejeon 301-721, Republic of Korea.
authors.forename: Sang Lyun
authors.initials: SL
authors.lastname: Nam
authors.affiliation: Department of Obstetrics and Gynecology, Chungnam National University Hospital, 282, Munhwa-ro, Jung-gu, Daejeon 301-721, Republic of Korea.
authors.forename: Jung Bo
authors.initials: JB
authors.lastname: Yang
authors.affiliation: Research Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Research Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea. Electronic address: sbrho@ncc.re.kr.
authors.forename: Seung Bae
authors.initials: SB
authors.lastname: Rho
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D002465:Cell Movement; D019938:Cyclin D1 / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D019938:Cyclin D1; D051417:Focal Adhesion Kinase 1; D024243:HMGB1 Protein; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C546842:MTOR protein, human; C496050:PTK2 protein, human
keywords: Anti-apoptotic function; BTB/POZ domain; FAK/mTOR signaling; High-mobility group box 1; Yeast two-hybrid system