TY - JOUR
T1 - HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells
AU - Yuan, Hong
AU - Kajiyama, Hiroaki
AU - Ito, Satoko
AU - Chen, Dan
AU - Shibata, Kiyosumi
AU - Hamaguchi, Michinari
AU - Kikkawa, Fumitaka
AU - Senga, Takeshi
N1 - Funding Information:
We thank the members of the Division of Cancer Biology for their helpful discussions. This research was funded by a grant from the Takeda Science Foundation and Ministry of Education, Culture, Sports, Science and Technology of Japan (Molecular Nanomedicine 2306 to TS, B:24390380 to HK and B:25293341 to FK).
PY - 2015
Y1 - 2015
N2 - Homeoproteins, a family of transcription factors that have conserved homeobox domains, play critical roles in embryonic development in a wide range of species. Accumulating studies have revealed that homeoproteins are aberrantly expressed in multiple tumors and function as either tumor promoters or suppressors. In this study, we show that two homeoproteins, HOXB13 and ALX4, are associated with epithelial to mesenchymal transition (EMT) and invasion of ovarian cancer cells. HOXB13 and ALX4 formed a complex in cells, and exogenous expression of either protein promoted EMT and invasion. Conversely, depletion of either protein suppressed invasion and induced reversion of EMT. SLUG is a C2H2-type zinc-finger transcription factor that promotes EMT in various cell lines. Knockdown of HOXB13 or ALX4 suppressed SLUG expression, and exogenous expression of either protein promoted SLUG expression. Finally, we showed that SLUG expression was essential for the HOXB13-or ALX4-mediated EMT and invasion. Our results show that HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion of ovarian cancer cells.
AB - Homeoproteins, a family of transcription factors that have conserved homeobox domains, play critical roles in embryonic development in a wide range of species. Accumulating studies have revealed that homeoproteins are aberrantly expressed in multiple tumors and function as either tumor promoters or suppressors. In this study, we show that two homeoproteins, HOXB13 and ALX4, are associated with epithelial to mesenchymal transition (EMT) and invasion of ovarian cancer cells. HOXB13 and ALX4 formed a complex in cells, and exogenous expression of either protein promoted EMT and invasion. Conversely, depletion of either protein suppressed invasion and induced reversion of EMT. SLUG is a C2H2-type zinc-finger transcription factor that promotes EMT in various cell lines. Knockdown of HOXB13 or ALX4 suppressed SLUG expression, and exogenous expression of either protein promoted SLUG expression. Finally, we showed that SLUG expression was essential for the HOXB13-or ALX4-mediated EMT and invasion. Our results show that HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion of ovarian cancer cells.
UR - http://www.scopus.com/inward/record.url?scp=84979917106&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979917106&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.3673
DO - 10.18632/oncotarget.3673
M3 - Article
C2 - 25944620
AN - SCOPUS:84979917106
SN - 1949-2553
VL - 6
SP - 1
EP - 12
JO - Oncotarget
JF - Oncotarget
IS - 15
ER -