Abstract
BBF2H7 is an endoplasmic reticulum (ER)-resident transmembrane basic leucine zipper (bZIP) transcription factor that is cleaved at the transmembrane domain by regulated intramembrane proteolysis in response to ER stress. The cleaved cytoplasmic N-terminus containing transcription activation and bZIP domains translocates into the nucleus to promote the expression of target genes. In chondrocytes, the cleaved luminal C-terminus is extracellularly secreted and facilitates proliferation of neighboring cells through activation of Hedgehog signaling. In the present study, we found that Bbf2h7 expression levels significantly increased by 1.070-2.567-fold in several tumor types including glioblastoma compared with those in respective normal tissues, using the ONCOMINE Cancer Profiling Database. In some Hedgehog ligand-dependent cancer cell lines including glioblastoma U251MG cells, the BBF2H7 C-terminus was secreted from cells into the culture media and promoted cancer cell proliferation through activation of Hedgehog signaling. Knockdown of Bbf2h7 expression suppressed the proliferation of U251MG cells by downregulating Hedgehog signaling. The impaired cell proliferation and Hedgehog signaling were recovered by addition of BBF2H7 C-terminus to the culture medium of Bbf2h7-knockdown U251MG cells. These data suggest that the secreted luminal BBF2H7 C-terminus is involved in Hedgehog ligand-dependent cancer cell proliferation through activation of Hedgehog signaling. Thus, the BBF2H7 C-terminus may be a novel target for the development of anticancer drugs.
| Original language | English |
|---|---|
| Article number | e0125982 |
| Journal | PloS one |
| Volume | 10 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2015 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
Promotion of cancer cell proliferation by cleaved and secreted luminal domains of ER stress transducer BBF2H7. / Iwamoto, Hideo; Matsuhisa, Koji; Saito, Atsushi; Kanemoto, Soshi; Asada, Rie; Hino, Kenta; Takai, Tomoko; Cui, Min; Cui, Xiang; Kaneko, Masayuki; Arihiro, Koji; Sugiyama, Kazuhiko; Kurisu, Kaoru; Matsubara, Akio; Imaizumi, Kazunori.
In: PloS one, Vol. 10, No. 5, e0125982, 01.05.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Promotion of cancer cell proliferation by cleaved and secreted luminal domains of ER stress transducer BBF2H7
AU - Iwamoto, Hideo
AU - Matsuhisa, Koji
AU - Saito, Atsushi
AU - Kanemoto, Soshi
AU - Asada, Rie
AU - Hino, Kenta
AU - Takai, Tomoko
AU - Cui, Min
AU - Cui, Xiang
AU - Kaneko, Masayuki
AU - Arihiro, Koji
AU - Sugiyama, Kazuhiko
AU - Kurisu, Kaoru
AU - Matsubara, Akio
AU - Imaizumi, Kazunori
PY - 2015/5/1
Y1 - 2015/5/1
N2 - BBF2H7 is an endoplasmic reticulum (ER)-resident transmembrane basic leucine zipper (bZIP) transcription factor that is cleaved at the transmembrane domain by regulated intramembrane proteolysis in response to ER stress. The cleaved cytoplasmic N-terminus containing transcription activation and bZIP domains translocates into the nucleus to promote the expression of target genes. In chondrocytes, the cleaved luminal C-terminus is extracellularly secreted and facilitates proliferation of neighboring cells through activation of Hedgehog signaling. In the present study, we found that Bbf2h7 expression levels significantly increased by 1.070-2.567-fold in several tumor types including glioblastoma compared with those in respective normal tissues, using the ONCOMINE Cancer Profiling Database. In some Hedgehog ligand-dependent cancer cell lines including glioblastoma U251MG cells, the BBF2H7 C-terminus was secreted from cells into the culture media and promoted cancer cell proliferation through activation of Hedgehog signaling. Knockdown of Bbf2h7 expression suppressed the proliferation of U251MG cells by downregulating Hedgehog signaling. The impaired cell proliferation and Hedgehog signaling were recovered by addition of BBF2H7 C-terminus to the culture medium of Bbf2h7-knockdown U251MG cells. These data suggest that the secreted luminal BBF2H7 C-terminus is involved in Hedgehog ligand-dependent cancer cell proliferation through activation of Hedgehog signaling. Thus, the BBF2H7 C-terminus may be a novel target for the development of anticancer drugs.
AB - BBF2H7 is an endoplasmic reticulum (ER)-resident transmembrane basic leucine zipper (bZIP) transcription factor that is cleaved at the transmembrane domain by regulated intramembrane proteolysis in response to ER stress. The cleaved cytoplasmic N-terminus containing transcription activation and bZIP domains translocates into the nucleus to promote the expression of target genes. In chondrocytes, the cleaved luminal C-terminus is extracellularly secreted and facilitates proliferation of neighboring cells through activation of Hedgehog signaling. In the present study, we found that Bbf2h7 expression levels significantly increased by 1.070-2.567-fold in several tumor types including glioblastoma compared with those in respective normal tissues, using the ONCOMINE Cancer Profiling Database. In some Hedgehog ligand-dependent cancer cell lines including glioblastoma U251MG cells, the BBF2H7 C-terminus was secreted from cells into the culture media and promoted cancer cell proliferation through activation of Hedgehog signaling. Knockdown of Bbf2h7 expression suppressed the proliferation of U251MG cells by downregulating Hedgehog signaling. The impaired cell proliferation and Hedgehog signaling were recovered by addition of BBF2H7 C-terminus to the culture medium of Bbf2h7-knockdown U251MG cells. These data suggest that the secreted luminal BBF2H7 C-terminus is involved in Hedgehog ligand-dependent cancer cell proliferation through activation of Hedgehog signaling. Thus, the BBF2H7 C-terminus may be a novel target for the development of anticancer drugs.
UR - http://www.scopus.com/inward/record.url?scp=84957599178&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957599178&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0125982
DO - 10.1371/journal.pone.0125982
M3 - Article
C2 - 25955804
AN - SCOPUS:84957599178
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e0125982
ER -